2, the only network with the full debate. with updates from the roll call group. . . . later, so we are releasing the

estimates today. by november 14, today up to which those estimates includes many times more children and younger adults, unfortunately, had been hospitalized or killed by h1n1 influenza that occurs during the flu season. we will cover vaccine supply, which is increasing access in many parts of the country and there is still a good window of opportunity to get vaccinated against h1n1. tomorrow we will provide you the update as we do each friday. it is likely to show that the disease continues to decline as the current wave recedes. flu season usually lasts until may. when we have asked flup experts

from around the country and around the world what they think will happen, about half think we will have more cases, about half think we won't. the truth is we don't know. only time will tell. vaccination remains the most important thing you can do to protect yourself and your family from h1n1 influenza. what we provided last month were the updates through october 17 based on the best available data from multiple data sources. what we have seen so far shows that people under the age of 65 are most heavily impacted by influenza. by november 14, many times more children and younger adults unfortunately had been hospitalized or killed by h1n1 influenza than happens in the usual flu season. specifically, there have been,

we estimate, nearly 50 million cases, mostly in younger adults in children. more than 200,000 hospitalizations, which is about the same number that there is in usual flu season for the entire year. and sadly, nearly 10,000 deaths, including 1,100 among children and 7,500 among younger adults. that's much higher. as we have seen for months, this is a flu that is much harder on younger people and fortunately has largely spared the elderly until now. what that means, if you calculate it is that about 15% of the entire country has been infected with h1n1 influenza and that means about one in six people. that still leaves most people not having been infected and

still remaining susceptible to h1n1 influenza. we are releasing today information on the burden of influenza among the american indian and alaskan native population. this is 12 states where half of the indian population resides. this is in this week's finding. the death rate is four times higher for this group. this is largely a reflex of -- a reflection of access to health care rather than genetic or race ethnicity difference. since the beginning of the h1n1 outbreak, we have been aware of the potential for greater harm in populations with higher susceptibility and prioritized

working with states to ensure in the health services and other facilities that care for american indians and alaskan naturetives get vaccines and treatment early on to reduce the burden of death within existing technology. vaccine supplies continue to grow. we added more than 12 million additional doses available in the past week. this brings us to 85 million doses of h1n1 influenza vaccine available. many states have increased the ellgict having met the -- eligibility and that is consistent with the advisory committee. this is entirely consistent with what's been recommended. we have seen an increasing number of states do this, sometimes in individual communities or counties within

states, sometimes in entire states. it is important as they have been doing at the state and local level to plan for that to get the vaccine out more widely to the pharmacies to a greater group of doctors. doing that has benefits. it enables who want to get vaccinated, but it increases the number of people in the high priority groups who get vaccinated as well since people with diabetes go to their doctors' offices and the more offices that have the vaccine, the more people at high risk as well as others will be vaccinated. this past week, c.d.c. consistent with policy began offering vaccine to all employees. and i will get vaccinated using the nasal spray vaccine in a few

days and we continue to prioritize the high risk groups encouraging those with underlying conditions, infants to get vaccinated in particular. this is still a good window of opportunity to be vaccinated. i can understand that many people might say, well there has been so much disease and going down, why get vaccinated now, but we don't know what the future will hold. during the flu season, you get vaccinated because the season will be bad, that's the situation we are in now. we are at the beginning of december. flu season lasts until may and we don't know what the future will bring. we might have a lot more cases, we might have few. and it's likely if there are more cases that it will be different in different parts of the country. it's a big country with different patterns of disease over the past season. so i hope that all who are

interested in being vaccinated will be vaccinated. it's the best way to protect yourself and families, serious hp hospitalization or -- hospitalization or death. less likely to have the third wave in the weeks and months to come. thanks very much. i will take questions starting in the room. >> thanks for doing this. two questions, could you tell us about what's going on with seasonal flu. is that starting to appear more? and also, you said you were going to get the nasal vaccine. why nasal? studies have shown that shots

are more effective in adults. >> in terms of which formulation to get, each year, the data will show one is comparable, i have a year to get the nasal vaccine so i figured i would get it this year. your first question was what? seasonal. we will provide that tomorrow, but we have seen very little seasonal flu. we are beginning to see influenza b. we did have a death in a child that is covered by the seasonal flu vaccine. the uptake has been fairly widespread and the supply is nearing its end for seasonal flu vaccine, but there is still some out there in some places. >> one clarification.

is this the same -- using the same methodology that you did in october? if we have 10,000 deaths now, that means there have been 6,000 in the past month? could you talk a little more broadly about how this compares so far with seasonal flu. i know the time period is different, but are you thinking now that this is taking a worst toll or less of a toll? >> so the methodology details are all given on our website. it's not quite that you can take the current estimate and subtract the previous estimate to say what happened in the past month, because there is some correction for late reporting. but there has been a lot more disease in the month that's reported than in the months before. in terms of comparison of this year's flu -- h1n1 with seasonal

flu, it is much milder for older people and less likely to result in death because older people are less likely to get infected, but it has been a much worse flu season for people under the age of 65, younger adults and children. the estimate we have -- the estimate that we are releasing here is not done in the same way that gives us the 36,000 estimate. that estimate is a different methodology and would give a slightly larger number than this number would give. if you were to compare, even though it's not directly applicable comparison, under 50, in that estimate, there are less than 1,000 deaths a year in age under 50. we didn't break out in this. but a large proportion of those 7500 adults are under 50. it is really many times more

severe in terms of severe illness and hospitalizations are several times higher for children and young adults in h1n1 than in a usual flu season. >> on the phone? >> thanks a lot. dr. frieden, in the report, the much higher mortality geas you will all the way back to 1819 pandemic. i'm wondering if anything is known about the genetic component of that risk and what the -- what the mechanism is, if it is the same for aboriginal

peoples or is that a mystery? >> there is a debate about the rate of disease is higher for flu and other infectious diseases. it is difficult to teas out the effects where nutrition is different in early childhood, access to health care, the likelihood of having an underlying condition such as diabetes, which is prevalent in many populations, particularly in the u.s. of american indians and alaskan naturetives. but the bottom line is the same, that vaccination is important. the scientific work of sorting that out i think still has a fair amount to be done. on the phone? >> los angeles times.

>> do you have any estimate of what proportion the number of native americans have been vaccinated? >> we don't have the data and it's difficult to get it. we do know that although there are large differences between different tribes in different areas, in many places, vaccine uptake is quite high. and in fact, some of the most important vaccine studies that have been done have been done showing the effectiveness of different types of vaccine in the population. next question on the phone? >> cnn medical news, your line is open. >> thanks for taking my question. my question is about h1n1 and homeless population. this is a susceptible population and i'm curious if the c.d.c. has any numbers on how many

homeless people have been infected or died? >> many people who are homeless fall into the higher risk categories because of underlying health conditions and in a homeless shelter, there is a potential of an outbreak. we have not seen as many outbreaks. we have seen more school-based and college-based outbreaks but they have significant medical needs and we want to encourage rapid treatment and if they are in a high priority group, vaccination and many states have expanded it to that group that should be vaccinated. >> your line is open. >> doctor, i wonder if you could have an estimate of what the level of population unity is for

h1n1 either by vaccination or infection and if you could estimate what the level of population unit it would take to prevent a third wave this winter. >> there are a lot of theories about what wouldn't or would prevent a third wave and how many people are immune now through either the vir rust or vaccination -- virus or vaccination. even if there were a lot of infections in people who didn't have symptoms, that leaves people without immunity. and it's going to be different in different communities. there are going to be different rates. within cities, there will be different parts of the city with different rates. what that means in terms of future cases is hard to predict. and the only certain answer is that only time will tell what

the future will hold, but we know that the more people who get vaccinated the lower the likelihood will be of more cases or third wave. >> on the phone? >> thank you for taking the call. the figures you gave earlier for hospitalizations and deaths include estimates since the virus emerged in the u.s. until october 14? >> first seven months of the pandemic in the u.s. any questions in the room? >> there have been a couple of developments regarding anti-vireals. would you mind speaking about that and also -- maybe i'm wrong but in the b.m.j. article that suggested that tamaflu is not as

effective. >> all of the evidence we have seen is consistent with our recommendations. we don't recommend it for routine cases of influenza in healthy people. we do recommend that people who have underlying conditions or people who are severely ill get promptly treated with anti-vireals because that will reduce it and we have been encouraged that in the sites, the proportion of kids coming in is much higher than it was last year so the message of early treatment of those with severe illness, i think, stands and is quite important to reduce the likelihood of severe illness or death. other questions in the room? >> fox 5 here in atlanta. can you talk about americans. how receptive are they and have

you done any polling? are you getting a feel of how many people are willing to get it? >> about half of the americans want to and plan to be vaccinated. this is a great window of opportunity to get vaccinated. >> on the phone? >> richard knox. >> thanks. as you may know yesterday, the ran corporation released a study showing that about the same number of people who are getting vaccinated has shifted forward in time. at the same time, you said in the past that there is more of a seasonal vaccine out there and you said a minute ago we are reaching the end of the supply. so i'm having trouble

reconciling those two things. >> we don't usually have coverage figures until the end of the season, but we know that a lot of seasonal flu vaccine was given and it was given earlier than has been given in the past. and we began hearing reports of shortages of seasonal flu. it is done in a very different way than the h1n1 vaccine program. the government is involved in the purchase or distribution of only about a tenth of the seasonal flu vaccine. most of that is in the private sector. we get our information from health care providers, surveys and from the producers of the vaccine in contrast to h1n1, where the vaccine supply is through the health departments. one more question on the phone and one in the room. >> "washington times."

>> i'm reading from the rand study where it says that 38% said there was no vaccine available when they tried. yet you indicate that supplies are dwindling and therefore they would have had a chance. do you have a feel of what that survey is about? >> i think there was more interest in seasonal vaccination this year than there has been in the past probably because of the attention to influenza generally and probably some people who wanted to get theñi vaccine. it's a challenge because when the manufacturers make more vaccine than there is demand, they have excess vaccine at the end of the year as has happened before. so it's something of a guess in terms of how much the manufacturers make and how much the market will bear. that's how the seasonal flu program runs, it's up to the manufacturers to decide how much

to make. the government only buys about a tenth of that, distributes it to public clinics. we have been providing more support for that. and one of the real benefits of the h1n1 experience has been our ability to reach groups that need to get seasonal flu vaccine every year in the future, including particularly school kids with lots of schools now having experience giving vaccine at school and women who are pregnant, with more doctors vaccinating in their office, as we hope many more will do. any other questions? >> i was just curious, is there a mechanism or the c.d.c. redistributing the h1n1 vaccine if you one outlet needs it or is that up to the states? >> many states are adjusting within counties, if one county

has more than another to address the level of demand. what we're seeing is as there is a big increase in the amount of vaccine available, doubling of the vaccine available in the past month, there are more opportunities to identify a vaccine that would be available in places with high demand. and we will be looking at that in the coming weeks. [captions copyright national cable satellite corp. 2009] [captioning performed by national captioning institute] >> we are looking live at the floor of the u.s. senate. this is the second weekend in the row that the senate is in session. last week, it was health care legislation. this weekend, fiscal year 2010 spending. right now, they are in the midst of a procedural vote. while they are not done with health care, work is continuing behind the scenes on the measure. formal debate expected to resume on monday. debate on our companion network c-span 2. we expect to hear from a number

of senators talking about health care. we plan to have that live right here on c-span. in the meantime, we'll show you discussion from today's "washington journal" on a comparison of health systems here in the u.s. and france. rench health care. guest: i have experienced this as a consumer on like many people to comment about health care in this country, talking about socialized health care. my wife is from so i go to france every year and use their health care system. my point is that on a consumer level, on blood level of going in and trying to get my back looked at, the french system is

much, much more rewarding than is the american system. i think people on the free market side of the aisle who have opposed a lot of democratic welfare proposals, i think that over the years, they have made a strategic error when they have said things like we have the best health-care system in the world. they say we are on the march to socialism. what they have missed is to understand how much health care insecurity in america is a fundamental problem. it is a problem that is clearing and needs to be fixed rate in america, was not able to get health insurance for more than three years. i may help the guy. this is such -- i am a healthy got. uy. they have missed the opportunity to push for market reforms and be part of that conversation

instead of now playing defense and arguing that we are going to cut medicare. part of what i am trying to do is to say we might have missed an opportunity. :ñalso, i think the best role f journalism is not to take the best -- the worst opinions of your opponents, take the best part ofñixd their opinion. host: as far as your back is concerned, what would be the ease of getting a doctor? guest: in france, you choose your own doctor. you always do. it is easier to get an appointment, there is notxd t0i third and fourth party complicated system. you choose your doctor, you go there, you pay on the spot.

i have had minor oral surgery at a cost me only 300 bureaus. and they apologized for it. they do a lot of health care through pharmacies. you could go to your local pharmacist and they will engage in a bunch of opinions. this is a level you cannot imagine that a cvs. there are licensing systems in the u.s. and lawsuits that people people on their toes. they don't have that in france. there is a direct consumer experience. that said, the reason why you only pay 300 euros is you are paying through the nose for taxes and other things which abnegate affects in france. as one of the reasons why my wife does not live there. host: a much of the tax structure is going into health care? guest: a significant amounts of they are trying to cut costs.

every time they do, they create a huge political incentive of french people who raise that as problems. their tax structure is much more onerous than ours. there's a mentality in france which is very un-dynamic where people look to the government to solve all problems. the health care system works better than any other part of the french state. unfortunately, they send the french state to places where it does not belong and recruits -- encourage it creates frigidity. host: we will take your calls are from the numbers on the screen. what about more serious cases

like cantor of long-term illness? our they handled? guest: what france does better is the fundamental advantage is that there is no insecurity. you wake up, you are born, you have health care. at american at any given time, scores of millions of people do not tell health care. we underestimate how much of an important deal that is. it does not bankrupt you and you move on. in america, the quality of the highest care is better. when i am 30 years old and i do not have many medical6ú issues d all i was catastrophic insurance, i would rather be in france. talk to me when i am 65 or 72 and i need an angioplasty or whatever, i would prefer to be in america for the procedure. the quality of the procedure is better than -- in america, not a huge amount better, but definitely better. in france it will not bankrupt

you. another difference is that in america because we have this clause i-free market -- quasi- free market, it is individual- you ask your doctor for an opinion you get a second opinion. in france, they tell you how things are with one opinion. host: you said your wife went to a doctor and some lumps were detected in a breast? guest: they tested in america and said no problem and she went back to france to one of the best doctors in france for these things and they said it is something that should be removed. a lot of care in america goes to what ever dr. you go to maybe in the network of they do not specialize in what you need and it is complicated. that was the case there in france. you go to a person that specializes in it right away and

they might deliver a better first diagnosis. host: guest is here from it -- until 8:00. our democrats line is next. caller: i make retiree from the federal government -- i am a retiree from the federal government and i have the same health program that the senators and the congressman had. this year, i am not allowed to have anything but the high- deductible health insurance. i do not have a choice. i am only allowed to have procedures listed in the manual. i think that is very poor and it is a lie and that that is what they're signing up the rest of america for, it is wrong. i don't think the states should have the power to say what federal employees can select.

i don't know about france but i am telling you it is getting worse and worse in america. it is all about the dollars, not about health care, at all. guest: i appreciate those, a big difference in america is that we have a natural kind of american allergy to bureaucrats getting involved in the intimate decisions in a way that france does not. you see this with the health care bill now. it is being held up periodically over questions of abortion. should federal dollars go to supporting abortion? that would not be an issue in france. they don't think that way. when you have bureaucrats deciding if we should have a natural reaction against it, it slows everything down host: our republican line is next. caller: a few years ago, there was a heat wave in france, very dramatic, in august i believe.

some 10,000 elderly people died. they talked about the problems with air conditioning in france. they also said something to the effect that doctors were handicapped by law'& seeing patients. can you shed light on that? guest: what i remember from that and it is terrible every time there is a big heap way. -- heat wave. in france it is worse than america. it was more[yu that people naturally depended or supposed that the government would take care of their grandparents. it was the mentality of the state takes care of everything so we don't need to call grandma and make sure she is doing okay.

air-conditioning and central heating are not quite as developed as they are here. i would be interested to hear more about the specific doctors being handicapped complaint. host: our emergency rooms in france? guest: i have not experienced it but it seems like it would be about the sameñi. the french are really good at stake-sector productivity. the british are bad at state- sector productivity. @@@@@@@ >> so they are good at that part of it but there are nightmare scenarios of health care schemes with emergency rooms are

nightmarish and waiting lines and all kinds of shortages. host: it was asked, does the french health system pay for doctors, hospitals? guest: most money i ever paid at a pharmacy was like $20. there is a built-in subsidy. but you do pay on the spot, which at least gives you the illusion that you are having a direct accounting for it. there's not this thing in america where you go there and pay a co-pay, wait for your insurance and get billed. i'm solving some kind of nightmare bills from 2006 now and i have no idea who's paying what and what's covered. in france, you pay on the spot. and usually that's it. sometimes reimbursement. not free, but you do pay out of pocket, a limited amount and

that's because of these massive subsidies. host: it is determined by each of the parties involved? guest: i don't know. host: as far as your experience with doctors, are there enough doctors to meet the needs in france? guest: i think so. there is an artificial cap on their salaries. they don't make a ton of money. if you watch michael moore's "sicko," it portrayed france as an unmitigated paradise and the doctors make a nice living. well, that's too much of a gloss of what happens there. but french doctors don't generally get compensated on the super high level but they seem happy. part of the reason is they don't have malpractice there because there isn't a big civil lawsuit kind of system as we have here in america and i would not advocate that for us.

guest: the cost is reflected in the cost of care and salaries. again, we can't exactly have that system here. host: new york on our democrats' line. caller: i work as a teacher and my health care costs many thousands of dollars for both myself. you mentioned that in france you pay through the nose in taxes for the coverage we get. if we switch that off and you are married to a french woman, how do you get that coverage?

and what does she pay? guest: most of her salary comes from france. she is a journalist and works for european publications, so that money is taxed on the front end. french taxes. this is the only way in which we benefit from paying french taxes is we get medical care when we go home for christmas. she pays for all kinds of state benefits and solidarity as they say there. by definition there is no way we can enjoy. so even as axd freelancer, ther is a large sort of tax deduction that comes from out of the money that you make on the front end and also you are taxed again sort of like on an annual income tax basis. host: no matter what income you make or don't make in france, you are covered by health care, regardless of poverty or

anything else? guest: yes. you can get supplemental insurance as well. but you are covered when you are born. host: atlanta. chris on our republican line. guest caller: this guys sounds like a socialist to me. guest: i tried to go live in cuba and didn't work out -- it's not socialist, communist. i lived in central europe for eight years and i saw, unlike a lot of people who throw around such accusations, i have seen the wreckage that communism can cause. i'm not saying we should do the french health care system. if you are going to oppose obamacare because i do oppose,

if you don't break the link between employment and insurance. when you have these state by state regulations that we have, you artificial choke off what should be a free or fiscal year market in health care and therefore you don't have the provision of choice and competitive pressure on prices. what i'm saying is we should not become like cuba or france or anywhere else, i recognize what works and doesn't work. host: what do the french doctors and the medical system think about our health care? guest: they say how can you live in a savage system and they say but there is a great new drug you have come up with. host: in your piece --

host: can you expand on that? guest: they say like, americans are complaining if we pass obamacare, you won't be able to choose your own doctor and waiting times, the fact is that is how it already is in america. when i go back to france every year, i engage with doctors to talk about the comparative things. again, the comparison isn't all apple pie and ice cream here and nails and rocks here. there are many parts about it that don't work well in france and ways in which doctors think is better. they like the competitive nature of america and where that leads

you in new medicines and new treatments and these kinds of things. but they don't understand the system in which at any given time, 30 million people are uninsured. host: brighton, michigan is next. stan on our independent line. [captions copyright national cable satellite corp. 2009] [captioning performed by national captioning institute] >> we go live to the senate gallery to remarks from senate minority leader mitch mcconnell on health care. >> you'd look good on the front page of the paper. >> i can tell everyone here in the room is so happy to be here

on saturday morning. well, good morning everyone. i think a couple of observations this morning would be timely. yesterday, we heard from both c.m.s. and cnn. c.m.s., center for medicaid and medicare services, the actuary reported that this bill will not bend the health care cost curve. i would call your attention to a letter, september 17, 2009, from six of our democratic colleagues, cole, mccaskill, and others, saying, quote, if we pass health care reform legislation without addressing the issue of health care spending, we will have failed. so c.m.s., the actuary, an objective person who does this all the time says that the

rebill doesn't pass that test. now, the other entity we heard from was cnn and i cite them as one example of growing evidence that the american people are opposed to this bill. we saw two weeks ago in a poll that there was a 9% more americans oppose the bill than supported it. we saw last week in another poll, 14% more americans oppose the bill than supported it. and then now we see in the cnn poll, 61% oppose and only 36% in favor. the argument i hear my friends on the other side are making or imploring their members to make history. many things have happened throughout history and many of them have been mistakes. if this bill were to pass in the face of the overwhelming opposition of the american people, having failed to achieve the goal of holding down health

care costs, it would be viewed as a historic mistake. let me turn now to you, senator. >> thank you, mr. leader and to pick up on that point. the american people are applying their common sense to this bill. they recognize if you increase the size of government by $2.5 trillion and cut medicare by $500 billion and create a situation where employers are forced to raise their premiums significantly, that basically you are going to create a system that doesn't work well for them. the original goal of this effort according to the president was, a, everybody should have insurance, b, that the cost curve of insurance should be bent down and c, people who like their health care should be able to keep it. what has c.m.s. concluded? they have confirmed the common sense of the american people. they have said number one, after this bill is implemented, 24

million will still not have insurance. they have said as the leader has pointed out that the cost curve will go up by $235 billion and they have said that millions of people will lose their insurance because of the fact that their employers will have to increase their insurance costs. one of the most significant things they have said is this and i will read it exactly. they have said that this bill will jeopardize seniors' access to health care. this is the quote -- quotes of the administration's actuary. providers for whom medicare costs are a substantial part of their business could find it difficult to remain profitable and might end their participation in the program possibly jeopardizing access to

the care for beneficiaries, i.e. seniors, that's a direct quote. 20% of providers will be unprofitable. hospitals and doctors' groups will close and seniors won't get access to care. and they are bankrupting a system which is bankrupt to begin with and will be unable to cover the seniors who are already participating in it and will force seniors out of coverage that they presently have today. and that's ridiculous. >> i want to pick up on the point that my colleague from new hampshire made, we have the highest concentration of seniors and this report says that health care for seniors is going to decline because there will be less providers, doctors, hospitals, others, who want to give health care for seniors. it's not health care reform if

the doctor's not in. if you can't find a health care provider, how is that reform? another report, this isn't budget neutral but a gimmick. you pay taxes for the full 10 creers and only get benefits for six years. here's your house, you want to buy it, start paying now but can't move in until 2014. and at the base of all of this, this was supposed to be a plan that cut the cost of health care insurance for the 170, 180 million americans and on the other side, provide access. now we find for seniors that access is going to be taken away. so we're going to raise the cost of health insurance, we're going to cut medicare, going to raise taxes, doesn't sound like health care reform. when i go back to florida as i'm going to do this afternoon, the people i talk to are very

concerned about this bill and they say don't vote for this bad bill and please don't hurt our health care. this weekend, we are ear here but not voting on health care and not having amendments to make this bill better, but here talking about budget issues. we are supposed to be working on the most important issue facing the american people. they can't even find our colleagues on the other side to go down and talk about this bill. republicans are chompping at the bit to talk about this bill. when they do come down, half of them are cite sizing this bill. we should do what the american people said, start over, get it right and take it step by step. >> my colleagues have talked about access and the findings from the actuary, telling us what we expected to hear in the first place. well, in the state of alaska,

access is beyond just a concern, it's a crisis. and it's been a crisis for a period of years. we are a rural state, remote. we don't have any medical schools, so we're not growing our own, if you will. and unlike my colleague here from florida where he represents a state that has the highest per capita of seniors, i represent a state, believe it or not, is the fastest growing senior population per capita in the nation. you might not have thought that. and what's happening? we don't have providers in our state's largest city who are willing to see new medicare patients. an anchorage, alaska has about half the population of the state and 13 providers who are willing

to take new medicare eligibles. we just got confirmation on monday that one of those 13 is dropping out. she says in view what's happening and what is happening with the reimbursement in view of what you all are discussing back here, i can't afford within my family practice to take on new medicare eligible individuals, so she's dropping out. so that puts us down to 12. this is a crisis. and so when we look at proposed legislation that does nothing to expand access that basically says, to die, you now have a card, an insurance card that gives you access, but there's no providers that are willing to take you on, what have we done for these individuals? now we've gone beyond the c.b.o. letters and what's coming out of c.m.s. and looking at the

actuary. we have gone to our state's think tank if you will. institute for social and economic research at the university of alaska and asked them, give us an analysis of the house bill and give us an analysis of what we have here on the senate floor. and what it comes down to is nothing good for alaska. this doesn't help us in a state where our medicare reimbursement rates are lower than medicaid reimbursement rates. we are only one of two states that are in that situation. there are all kinds of unique factors, but the bottom line is, this increases the premiums for individuals, 10% to 13%. it crowds out those who are on medicare. it decreases access. it increases your taxes and at the end of the day, there's nothing good in this legislation for alaskans. they are saying we want to see change and reform, but this is

not acceptable to us. we've got to start over. >> any questions? >> senator, if as expected, the democrats attach the increase in the debt ceiling to a defense spending bill and don't allow you to have a stand-alone vote, will you vote against the defense spending bill? >> well, the issue of raising the debt ceiling is something that senator gregg knows a lot about and i know there is unrest among democrats about raising the debt ceiling without some mechanism to address this issue in coming years because we are drowning in a sea of debt. i'm going to ask senator gregg to talk about the proposal that may be in the works and a number of democrats who are themselves resisting raising the debt ceiling unless some mechanism is put in place to address the long-term, unfunded liabilities.

>> i've read that the proposal is to raise the debt ceiling by $1.9 trillion, which is reallyñ -- it's so startingly irresponsible and political that it's hard to come up with words to describe it. obviously, we don't need that type of an increase. the only purpose of it is to get us past the next election. it you is like drunken sailors saying we don't want the bar to close. they are spending like drunken sailors and not responsible to the american people about the debt they are putting on the backs of our children. and raising the debt ceiling, you are trying to push that off into the future. our position on our side of the aisle is we would like to have four issues raised. we would like to terminate tarp. this is becoming a piggy bank

for this administration for interest groups. all tarp funting goes to the debt unless it's repaid and what they are proposing are things that won't be repaid. the stimulus package spending up beyond a certain date, we haven't picked a debt yet, but maybe the end of next year, should be rescinded because it is well past the recession. we are giving money for certain prapetors and about 40% of the stimulus package will not have been spent by the end of 2010. third, there should be a freeze, freeze plus one, freeze plus two on discretionary spending. and fourth, something like the conrad-greg commission, which has 32 sponsors, 12 of whom are democrats should be taken up and voted on also. we would like to see that as part of the vote. i don't know how they are going to structure this.

it would be irresponsible if there was a vote on it. >> why would you vote for the spending bills in the appropriations committee and then vote against them when they're on the floor? >> my view is we should move the process along out of the appropriations committee and that has been the tradition, but when we get to the floor we hope they would be corrected and reduced. >> do you take them seriously? >> the process is important of proving all the appropriations bills. but i do believe that when you get to the floor, they should be drawn back. i would support across-the-board cuts on all those bills. if we could get the vote, but unfortunately, we aren't being allowed votes. >> all three of us are on the appropriations committee. we voted against it, 12.5% increase at a time when we are running debts up as senator

gregg pointed out, like drunken sailors, in a year we passed a budget without a single republican vote, that would double the national debt in five years, triple it in 10. at least we would have exercised some restraint over discretionary spending and that is why we voted the way we did. >> in your discussions with the majority leader do you get the impression we will see votes on the health care? >> they can't close down the bill. they have serious problems. the american people are almost screaming at us, please don't pass this. they have all kinds of internal problems. my assumption is, we'll go back to the bill on monday and start voting on amendments. that's what we should be doing, that's what the american people expect us to be doing. the anxiety level on the other

side is quite high. i think no one any longer believes this is inevitable. and next week will be interesting. >> follow up on that question. would you be willing to vote against the.bill if you don't like the other packages that come along with it? >> we are working with health care. we're going to see how they put the package together and take a look at it before making any final conclusions. thank you. [captions copyright national cable satellite corp. 2009] [captioning performed by national captioning institute] >> senate minority leader mitch mcconnell and others on health care legislation this morning as the senate continues working behind the scenes on that measure. debate today in the senate is on fiscal year 2010 spending. just a short time ago senators

voted 60-34 to limit debate on that legislation. a vote is expected tomorrow. senator john mccain talking about fiscal year 2010 spending. there might be remarks on health care this weekend, formal debate is expected to continue on monday. you can watch the senate live on c-span 2 of the. >> the health and human services department hosted a seminar friday on government research and development of new flu vaccines. speakers include h.h.s. secretary and the director of the national center for allergy and inif he can issues diss -- infectious diseases. from the national institutes of health in maryland, this is about 2 1/2 hours.

>> good morning everyone and welcome to n.i.h. i'm bill haul with the office of public affairs at theñi departmt of health and human services. i welcome you today for this seminar, media and public on new flu vaccine technologies. we have arranged this session today to offer the media and the public an opportunity to have a little more time to learn about the new technologies that flu vaccine technologies that our department through a number of our agencies have been working on as many of you have seen in the news about vaccine or h1n1 vaccine, it has been produced through our tried and true method of using eggs, which has a number of downsides to it. and so we have been working for some time now to develop new

technologies. . after this is over we will be

take the video of this and archiving it on the web along with a transcript of what's said here today. and if we can we'll put up the slides that we have as well if that's possible. so that should be up within a few days after today's event. so again welcome. and i'd like to get us started today by having sort of an overview and welcome by the director of the dr. francis collins. dr. collins. >> thank you, bill. good morning, everyone. welcome to those of you attending here at n.i.h. -- it's a pleasure for us to host this discussion about vaccine preparedness and new contingencies to put together ideas for the future, many of which are quite exciting about i was in which the development of future vaccines for influenza and other infectious agents is actually a very rapidly-moving field in the scientific arena

and which you will be hearing about in the course of this morning's presentation. happy to be able to host this seminar just h1n1 summit that was held here at n.i.h. back in july. at that point president obama put forward a four pillars to a plan that are constantly being revised and reconsidered. those four pillars are surveillance, secondly community mitigation measures, third vaccination, ourxd main topic today, and fourth communication which is also an important part of today's activities. we've learned a lot about the courset( of h1n1. over the course of the autumn as it returned to this country, and we have learned how to adapt the plan to conditions and staved off some of the worst case scenarios although as everyone knows we've also struggled with availability of sufficient doses of the vaccine because in part

of its slow growth in eggs which is one of the reasons i think many people are interested in hearing about other approaches in the future. i think being here at n.i.h., it's important to point out the very hard work that was done. and i'm sure you'll hear more about that this morning and under dr. fauci's capable leadership the efforts to test the vaccine and show in fact it is a highly-effective vaccine and that we know a lot about that based on the clinical trials that were conducted quite rapidly, including on adults and on pregnant women and on children. so our present position of certainty about vaccine effectiveness is based upon that very rapidly-moving and rigorously-conducted research. so it's fair to say we have in this particular pandemic achieved confidence that we have a safe and effective vaccine, but we've also learned, as if we

didn't know it already, that technologies used to produce that vaccine based upon methods that have been around for a long time could certainly use advances for the future and to take full advantage of the scientific progress, that's what we'd like to talk about today. so this seminar is really focused on how far vaccine technologies have progressed and where they may need to go in the future. we have a variety of expert speakers who will be presenting to you today. bruce gellin, gary naibel, karen highman and tony fauci whose leadership in this whole area over the years has put the united states in a position of international prominence in terms of the technology and the way in which vaccines can both be developed and tested. so i think it's going to be very interesting morning. and again i hope those listening on the web will feel free to send in questions through that address that was mentioned a

moment ago so there can be a chance for back and forth including people in the room and people beyond the room. finally i'd just like to say thanks to the secretary, secretary sibelius, who could not be here this morning but who has currently played a critical leadership role over the course of these many months of pandemic flu. she made a joke about how she didn't expect to have a pandemic in her welcome wagon, but she has adapted to that i think quite brilliantly. and i'd certainly like to give a great deal of credit to her leadership in pushing the agenda forward and making sure that all of the areas that needed attention got that kind of attention. she wanted to be here with us today but is unable because of other scheduled challenges. but she did prepare a special message that i hope will appear momentarily as we queue up a d.v.d. with that message. so without further adoption my boss, secretary kathleen

sibelius. >> thank you, francis, and thank all of you for attending this seminar on new vaccine technology. i think you're going to be very pleased you took the time to join us today. the presenters you are about to hear from are the leading experts from h.h.s., n.i.h. and the f.d.a. and the importance of the topic couldn't be more timely. the flu vaccine we used to is extraordinarily safe, it's extremely effective. it's the same flu vaccine we've used to immunize 100 million americans annually for decades. but processesome and outdated. we couldn't have had a better indication for the need for new flu vaccine technology than our experience with the 2009 h1n1 virus this mall. the flu vaccine's active ingredient is grown in chicken eggs. and like the influenza virus itself, it can be temperamental and unpredictable.

this year, when we needed manufacturers to ramp up production quickly, the antigen decided it would take its time. but even before the first outbreak of h1n1, we've known we needed to develop new technologies that will provide vaccine with the same level of protection but with a 21st century ability to meet the demand. it will be several more years before we're able to wean ourselves away from egg-based vaccine, but we're committed to moving ahead with 21st century vaccine development. ultimately, these efforts will help not just the united states, they'll help the world. and when the next pandemic hits, we'll be better prepared to mount a speedy, agile response. in the meantime, although we clearly don't have vaccine in the volume we'd anticipated. we know we have a safe and effective vac american people can count on it to provide protection from the h1n1 virus.

thanks again for coming. >> thank you, mad amount secretary. without first adieu i think we should move into the agenda for the program. that involves the first presentation from dr. bruce gellin -- from h.h.s. >> dr. collins, thank you for hosting us today. thank you for coming and for your interest in this tropic. i'm going to talk in the broader relief and some specifics about flu as well but wanted to give you a broader vision as well. you know, we all are quite familiar with what vaccines have accomplished. this is a slide that probably everybody at c.d.c. is required

to show in every session. i happened to borrow this one from dr. fauci as you'll see several of the slides of dr. fauci's in my set. >> in the past we wrote down u.c.i., unusual childhood -- usually childhood infections. -- another of dr. fauci's slides, it really features a few components of how we get to the ability to actually have these vaccines and have these impacts. we're accelerate the

technological advances and taking advantage of what technology may be available, not necessary lit once that are directed against specific diseases but those that can be applied to those diseases and vaccines. to design vaccines forly among the infections that don't have vaccines against them that -- and then the work on understanding the immune system and its response feeds into the development of vaccines both in terms of safety and effectiveness. of the many slides of the doctor's i have this i think has been my favorite over time. he keeps advancing it. the point here is really the convergence of break throughs in technology, basic science and their applications to the development of vaccines that can have these kind of impacts on the population. so you can see some of the many milestones that have occurred, obviously the germ theory is no longer a theory. there are many things along the way. and you're going to hear about some of these later on about some of these specific

developments that are going to be applied towards new vaccines. but you can see that it was detoxcation techniques, the availability of tissue culture, and now novel delivery systems give us whole new opportunities for developing vaccines. so we're going to focus more obviously the rest of the day on influenza. and i think when i look at influenza, these are among the many key ingredients. so we have the egg, the -- this is a poster from world war ii that was really the burden of illness in world war ii. it's hard to read, but basically there is the calculation of the absenteeism and the impact that had on the war effort. so whether it was inclusion from this was one-third of all the men and women who were lost these days were making tanks, a third making bombers and a third making rifles, there you see the number of tanks, bomberrers and rifles that wouldn't be made. sort impact that influenza has in the variety of sectors in society. so this is just a brief snapshot of some of the history of

influenza vaccine and of influenza vaccine. and you can see how there's a convergence of various parts of science that allow things to come together to kind of products we already have and the kind of things we'll have into the future. in the late 1928 was the first time axd virus, an influenza vis was identified from swine. separately in nashville dr. goodpasture was working on viral techniques. we found the fertilized egg was a great place to grow viruses. started working on other viruses, and ultimately influenza found its home there. in the early 30's, flu was isolated from humans. there were animal models that transmissibility. the ferret as louis pasteur said chance favors a prepared mind. because it was in a situation where people new england were working on the distemper vaccine

that a lab worker with influenza came in and infected the fer res which is the first identification of ferret as an animal model. later on world war ii as you said before accelerated the development of a vaccine because the military was very concerned about what the losses were in world war i with the pandemic and wanted to try to protect their troops. and then later on was the first influenza vaccine was approved for use. and in the 40's and 50's there was work on oil and water emulsions where at that time even applied to influenza it was clear that the ant body response could be improved, the height of the response was greater, the duration of protection was longer and it was a broader protection as well. that field apparently stopped when there were problems with local side effects andsists andster ill absences. but some that we'll hear about later had its history in the basic science es. separately by virus cultivation

moving from eggs to mammalian cells, 1954 december 11th was [inaudible] nobel prize lecture about tissue culture use for growing polio viruses and all the things that came from that. so again point of this is there's obviously a lot of conversion research that has the opportunity to come into vaccines. this is a wiring diagram of the vaccines. the vaccine and immunization system. and there's a lot more to it than the research compelling us. there is the surveillance aspect, there is subsequently when the vaccine is used how it's monitored, the interests in that, public perception to vaccines, the whole finances around vaccines. but just to give you a sense what we're talking about today on research, development, licensing and manufacture sits within this broader system. i raise that because it's the broader system that's a large part of what i've been working on at the national vaccine program office in developing a national vaccines plan.

last year we host add draft plan a lot of people have had a chance to look at. it was really a strategic focus for the nation's efforts to improve disease prevention and enhance vaccines safety. there are five broad goals in this plan, again many converge what we're doing today. primarily the first goal of developing new and improved vaccines but also the goals include vaccine safety, communication, education and decisionmaking, the programatic aspects of vaccines supply and delivery and global aspects of vaccine immunizations. later the institute of medicine will release a report that we asked them to conduct to give us an external view of what the priorities should be for our national vaccines plan as we move into the future. so we'll be hearing more about that as we finalize the plan. finally i think also to take us back to a different point in time, in 1978 in -- lewis thomas had this quote which was included in the 1994 plan. and i think if nothing else

we'll be looking for a new quote on the inside cover of the updated plan. but in 1978, louis thomas wrote that real high technology of medicine is the kind that is so effective that it seems to attract the least public notice. it has become to be taken for granted. this is generally decisive technology of modern medicine ex emfied best by the modern medicine of immunizations. things have changed since 1978, and we look forward to hearing more about some of the changes later today. thank you. >> thank you, dr. gellin. unless there's any specific questions at the moment we will have a q and a session after the next few speakers. we'll have a little bit of time set aside for that so dr. gellin can address those then. our next section looks at basic clinical and research activities going on here an add n.i.h. and n.i.h.'s funding of granting institutions around the country. so i'd like to have that started

off with dr. tony fauci, the director of the national institute of allergy and infectious diseases. dr. fauci. >> thank you very much, bill, and welcome all to the n.i.h. for this what i hope will be an interesting seminar and discussion. what i'm going to do over the next few minutes is to give you an overview of the advances that are occurring and that are planned in the technology of influenza vaccinology. this first slide which may seem a little bit complicated to those who don't have a habit of looking at the structure, the schematic structure of viruses, but it's very important. because you're going to be hearing from several of my

colleagues and myself about certain aspects of this particular diagram here that will be relevant to what we call the new platforms of vaccine technology for h1n1. this is the influenza virus. it is a r.n.a. virus. the r.n.a. codes for a number of important proteins. the one that's most familiar i believe not only to this are the hemoglutein and [inaudible] which give the influenza its h and n for the purposes of today we're dealing with the 2009 h1n1 pandemic influenza designated by a subgroup of this h and this a. but there are also other important proteins that could be potential targets for vaccines that i'll very briefly mention. the matrix protein, the nuclear capsis, m protein and ns 2. all of these here are potentially important and i'm going to spend a minute or two

on one or more of them over the next few moments. but i want to make this the background of what you're going to be hearing a lot of over the next hour or two from individuals. having said that, the h and the n become important when you designate the differences from season to season what we call seasonal influenza which as i'm sure most of you all know, results from very slight changes which we refer to as drifts. mostly in the h and occasionally in the n. these are predictable annual occurrences every year like clock work we have seasonal flu. there is residual immunity in the population which means the change is so small that even if people don't get vaccinated and it gives me chest pains to think about saying people don't get vaccinated. but if people don't get vaccinated, there still is a bit of residual immunity in the population, sometimes substantial, that what when it does drift you don't have a

public health crisis which is the reason why from season to season we don't have the kind of intensity that we're having now when you have a shift, namely a change that's completely different from previous years. this is different because it's unpredictable and it's rare. we've only had three of them in the 20th century. importantly, the population for the most part is naive because with some exceptions, a few exceptions, they have not knot seen anything that is closely related to the h or the n of the new pandemic. where does vaccination come in? there's no doubt in any public health officials armament of discussing influenza that vaccination is clearly the most effective method for preventing influenza and its complications. we have at our disposal a conventional influenza vaccine production capability which as you've heard many of us say is tried and true, namely it's

decades, it's worked, it gives a vaccine that's safe and that is quite effective. and we have a long history of that. however, there are some down sides of that which we've actually experienced this year of what we're going through now. namely, it is slow, it's inflexible, it requires a large supply of fertile chickens, eggs, stringent conditions, and importantly -- and we've seen this in spades -- it is entirely dependent on the growth characteristics of the virus that you put into the eggs. and we've gotten hit with that this year with a slow-growing virus. so let me very briefly go through the timetable of what happens. you know on a seasonal flu, put aside h1n1 for a moment, right around the end of january and usually the very beginning of february a decision is made as to what viruses will go into the trivalent vaccine that will be used in the united states and

worldwide. that occurs there, production begins, and over a period of several months, usually six to sometimes eight months, you have a variety of processes that go to the production, the filling, the packaging, the release, and then vaccination usually begins in the fall. i hope when we get to the question period we can talk about the inflexibility that came back to bite us this year when we had to start late in april instead of the end of january and instead of having vaccination beginning with the flu usually peaking in december, january and february, we got hit with the flu the moment the children went back into school at the end of august and the beginning of september. so what happened historically that prompted us, interestingly, not eight months ago or six months ago, but several years ago that we had to bring influenza advance enology into the 21st century? there was a threat of the h 5 n

1 pandemic in 1977 that is still smoldering but never material israeled. we had anthrax -- in 2001 so the whole idea of the biological catastrophe as our nation to respond was brought into sharp relief. then in 2004, some of you may remember the fragility of the egg-based culture became very, very clear to us when a production plant in liver pool cut out about 50 million doses that we were expecting because of a contamination problem. sort trek toward bringing the technology with new platforms began. and i'm going to spend the rest of my several minutes just talking a little bit about this. i want to make sure people understand the difference between improving production and search capacity versus new vaccine platforms. in other words, better ways to grow the virus versus a brand-new platform. and i'll explain what i mean to that in a moment.

also there's dose optimization strategies. and then finally a word or two on universal vaccines. all of these will also be discussed in some detail by my colleagues. i want to give you the 40,000-foot look at that. let's take a look at improved production in surge capacity. influenza vaccine production, when you grow it in eggs or grow it in cells, the one thing it requires is that you have to grow the virus. it's much more controlled to grow it in a cell culture as opposed to eggs aids which we've done for decades because you have more control over the amount of cells,er you have vastness of cells, you cknñ pull them out of storage, inok ate them. you have more control. you cut off abátu weeks not months. people mistakenly think if you go to cell-based you'll get it in a month and a half. it will be a little bit quicker but the thing about it is the

surge capacity is much more flexible. as you know, we're making the transition as you'll hear again from others from egg-and based to cell-based. it will be gradual and take a few years but we ultimately will get there. the important thing i want to emphasize mostly during my time is new vaccine platforms that allow for more efficient manufacturing of potentially better efficacy. i have five representative ones here. i'm going to spend a few seconds on each to set the stage for the more detailed one that you're going to be hearing from the colleagues that will follow. let's start off with d.n.a.-based vaccine. very simple. you take the genes of the particular protein you're interested in. when you grow the virus and you inactivate it, if you make it attenuated, what you're really interested in is injecting the h and the n. you happen to do it with a whole

virus. you can do it in a much more precise, pristine way by getting the gene of the h and the n, putting it into a plasma bed which is a vehicle to insert genetic material, put it in and inject it directly into the host, into the arm of an individual. it goes into the muscle and then it starts coding for the protein and prevents the hemoglutein on a human cell that's histocompatible because it's right in the person's arm it. creates a very efficient way to call upon the immune system to respond. why? because that's exactly the way we respond to ant jens, newt gingrich way, namely it gets presented to the -- any way. these are in various stages of development, not quite ready for prime time at all for influenza but it's something you'll be hearing from gary nabel and

others. the other is a subunit vaccine. we've spoken about that and i'm sure in the press you've heard about it. because one particular company is pretty far advanced in that. what do we mean? a little bit of a different twist. again, you take the gene, in this case of the hog, and you put it into what we call a vector in. this case and one example the vector is i insect virus which means it's a virus that infect insect cells. it happens to be a bacula virus. now you have this vector carrying theñr gene of the hedge hemoglutein. then the protein starts getting spitted out. you purify it and then you have instead of the whole virus you have the protein that you're injecting which induce as potent

immune response. we also have what we call microbial vector vaccines. that means you inject the vector itself with the gene directly in the person. what do we mean by that? instead of putting the gene into the vector and let the vector then make a lot of protein, you stick a vector like a benign, typical safe adital virus which is a common virus that infect humans, you take the influenza genes, you stick it in and you have what we call a recome bit ant vector. so this very harmless virus now is expressing the proteins that you want to make an immune response against. in this case, the hemoglutein. there's also virus-like particle. same principle. you take the genes and you could do the hog, neurobased or n 1, stick it into the appropriate vectors as we did before, you put it into cull it. and because you have so many

elements of the virus, lucky for us which happens sometimes is that these proteins assume what's called a virus-like particle. so it's an empty virus. it doesn't have any genetic material. but it has the proteins arranged the way they are arranged in the virus itself. that's called a vy virus-like particle. then you have synthetic pep tide. that's pretty simple. you could have pep tides, ame yo acid make pep tides, pep tides make protein. they're building blocks. we now have very good capability of synthesizing these pep tides to make them exactly how we want them,, for example the pep tide component of the hemoglutein. those are five representative new platforms. you'll hear more about that from the others who follow me. a very brief word on dose

optimization schedules. what we call adjuvant. very simply what it is is a compound that you give together with the vaccine protein or the vaccine as a whole virion. what it does, not only does it boost the immune response to reduce the amount of antijen needed it, gives a stronger, more durable response. we also know from experience that it widens the breadth of the response so that you have more cross reactivity. and there are a number of new adjuvant which are being worked on in a number of sectors including by n.i.h. grantees. i want to close by mentioning an universal vaccine which in my mind and in the mind of many of my fellowñi scientists and publc health officials is really the end game answer, not only to pandemic flu but to seasonal flu. it's something that isn't

immediately going to be available to us, but i believe strongly that it's doable. so let's get back to my original slide. there are targets for an universal vaccine. it's universal because it doesn't change from virus to virus, be it drifted seasonal or shifted pandemic. and the ones that are most important targets are the hemoglutein, maracaibo and mp protein. this is one example. you'll see beautiful slides from gary nabel of the h.a. protein sitting on top of the cells that has a component of it so the ha exists as a bold and as a stem. it has a component to it that just doesn't change much at all from virus to virus. and if we can get this in an

immunogenic form, which isn't ease yes, then you have the first step towards what we're calling a universal vaccine. and there's a lot of work going on in that. so i'll close with this last slide. even though this has been prompted by the need to respond better to threats like pandemic influenza, it should have been clear that everything that i'm talking about and that you'll hear from my colleagues relates not only from pandemic influenza but for something that is highly predictable, seasonal flu. so if we get the platform advances that we hope to get from the research that's going on now, we will have solved the problem that's unpredictable as well as one that's imminently predictable. thank you. >> thank you, dr. fauci.

we'll hear from our next two speakers thunder we'll take q and a from those in the room and on the web. our next speaker will speak about influenza vaccines the next generation. dr. gary nabel director of research center at the institute of ailery and research diseases. dr. nabel. >> thank you. what i'd like to do is to share with you some of the perspectives that we have here at n.i.h. i direct the vaccine research center. and what we're trying to do in our efforts here is not so much prepare for defendant distribution of vaccine -- prepare for direct defendant distribution of vaccine against this year's flu, but ask them the question what can we do in the coming years so we don't have to suffer through the same set of circumstances that we did during this time. just to give you an introduction

to the vaccine research center, we're low kate here on campus. just to orient you an overview of the n.i.h. from an aerial perspective, we're over on this end of the campus here in building one. the r.c. is over on the other side here. this is the clinical center. and so between the basic research that we have here, the clinical research that we have and even our colleagues at the f.d.a. who were essentially across the street from us, we really have the capacity at the n.i.h. and in the department of health and human services to do the full cycle of product development, at least from its earliest stages and basic research at the vaccine research center. we have a small pilot plant where we can make vaccine lots for clinical trials, particularly phase one through phase three clinical trials, test them in the clinical center, look at the immune assessment and basic scientists

as well as the clip eggses who can help make this -- clinicians and get us to that next generation of vaccines. what i want to share with you in the talk today are essentially three areas where we're working and where i think it's abundantly clear that scientific advances are really create some great opportunities to improve future influenza vaccination. i'm going to mention to you some of the work on development of vaccines for previous pandemic viruses no longer in circulati circulation, spes ficly the 1918 flu virus you're all well familiar with. this notion of preemptive vaccine using our knowledge of virus predicting its evolution from what we understand about the constraints on this virus in humans to prepare vaccines in advance of an outbreak so that we can get started in a more facile many time frame as

dr. fauci mentioned in his talk and as one of the constraints of our current vaccine development pathway. and finally, the prospects and progress in universal flu vaccines. and i'll go through all of these briefly. first of all, we know that clearly there was the great influenza, the 1918 spanish influenza. and one of the problems at the time is that we couldn't at that time we didn't even know the eatology of the flew when it occurred. so naturally any thought of a vaccine was out ofñi the questi. but thanks to some of the work here at n.i.h. from some of the intramural scientists, jeff taubenberg in particular it's been 1918 influenza virus. so what we've been able to do at the vaccine research center is to take some of the new technology specifically the d.n.a. vaccine technology that dr. fauci just described to you and ask, going back to the gene from the 1918 hemoglutein gene,

if we use a d.n.a. vaccine to immunize in this particular instance this was done in experimental animals with either the naturally-occurring hemoglutein or one that contains a small mutation that might make it a little bit less likely to create a problem if anything should recombine, would those confer protection against animal that is were challenged with the same 1918 lethal strain. and you can see that results here are quite clear, if you look at survival of animals that have been challenged with the 1918 virus if they were vaccinated with either one of these d.n.a. vaccines they were completely protected whereas the control animals were all -- all succumbed to infection in less than a week. so a new technology applied to an old problem suddenly gives us an opportunity to control it. you may say, why worry about 1918?

it's long gone. concern. for example, one of the more recent findings at several laboratories is now recognized is that there is in factçó cross reactivity, cross neutralization between this year's 2009 virus and the 1918 virus. and in fact, immunization with this old 1918 hemoglutein will protect against the 2009 virus. so had we known this in advance, this is again one of those technology that is we might have been able to employ to help us in that regard. now, in terms of predicting the future of flu, our knowledge of influenza virus is really advanced tremendously, particularly in our ability to look at the genetic changes that occur in the virus and also to understand the structure of this virus and how that relates to its ability to infect cells. now, i'm going to just take a minute to go through this

diagram with you. because i think it's essential both to understanding preemptive vaccine and more importantly in the last part of the talk the universal flu vaccine. the receptor of the hemoglutein of the virus is responsibility for its attachment to and infect the cells that it's going to infect. it's a trimeric protein. you can see in the red, green and gray colors, the three different components of that hemoglutein. they're all the same but they just come together to form a trimer. at the top of this particular protein is what we caught receptor binding domain. that's the part that cox onto the cell that will be infected. at the base is the stem and the stem is the region that undergoes rearrangement. that's responsible for fusion to the target cell. so we know that this is the part of the molecule that has to attach to the receptor. and if we magnify that region of the protein we see that there's

kind of a canyon and ridge structure. and we know that this is the region that actually binds to the receptor. and in fact, when we look at the avian influenza, we know that avian influenza that as tony mentioned has been smoldering throughout the world it hasn't transmitted to humans because it hasn't adapted to recognize human reaccept tors. but what we can do, knowing the genetic changes that occur in this region and knowing the structures here, we can actually change these deliberately in the laboratory. and we've been able to do this so experimentally we know how this virus has to change in order to adapt to humans. and in a paper we published in 2007, we actually began to generate some vaccine prototypes where we could in advance begin to prepare for the possibility that that jump might occur. and it would allow us to approach vaccine design in a

prospective way that would leave us better prepared for a future outbreak. finally to get to the issue, the very important issue and i think the one that we all are working very hard on with respect to universal flu vaccine, let me take a couple of slide to give you some perspective. the yearly flu vaccine that is we now receive require that we prepare new vaccine lots every year. that's anywhere from 120 to 150 million doses. that number has increased recently. and it actually results in an expenditure of between 2.8 and $4 billion every year just to generate those vaccine lots. so that's quite an investment of time, effort and expense. and the question is this, can we make a better vaccine. can we improve the poe ten circumstances can we enhance its breadth? and in short when we talk, could we make a vaccine that would be used in the same way we would

news measles, mumps, rubella, chickenpox, make a vaccine that would be administered in childhood and last a lifetime. the we won't get there in one step but i'd like to share perspectives on how we are hoping to get there and why there's some reason to be optimistic. again as dr. mentioned in his talk, there are a number of different proteins within the influenza virus that are highly conserved. and so when those particular proteins are highly conserved it means that if we're able to target them they won't change from year to year and they might serve as better targets. and both in our laboratory here at the vaccine research center as well as a number of extra mull laboratories that dr. hellmann will describe to you in her talk, a number of different strategies are being used to immunize using gene-based vaccination strategies where again as dr. fauci mentioned, we insert only the genes for these proteins

into d.n.a. vectors or viral vectors. what we then can do is to do a combination of priming and boosting strategies with these vectors to stimulate t-cell responses or in some case ant body responses to these highly conserved proteins. here's an example again published in a paper in journal vy rolly a couple of years ago where we did this kind of vaccination approached, gene-based, protein, we then challenged them with an avian that is highly fay stall in animals. -- they provided complete protection against lethal challenge in these models. so this is one model that is being pursued by a number of groups to get us to an universal vaccine. there's another target that tony

mentioned in his talk and i think one that we're all very intrigued by and where there's a lot of effort, and that's the hemoglutein. the question is, is there a structural base that's to -- here again we benefit from our knowledge of the virus. what i'm showing you on this slide is a -- now the flu trimer that i showed you earlier, the try per kind of buried here below. what you see above are these dimeric proteins. these different proteins are actually only antibodies that neutralize influenza. so what you're seeing is the docking points for these influenza-specific, these are strain-specific antibodies. these are the kinds of antibodies that we would generate from yearly vaccination that would actually protect us against a flu infection, for example like the 2009 virus we would be generating antibodies to these regions of the virus.

but as you can see, what i've shown on this particular slide, in red this is now a different diagram of the receptor where i use essentially space-filling models so you're seeing a more compact structure. and in red, i've highlighted the amino acid that changed among either the h1n1 viruses or the h 3 viruses. you can see all the changes in the hemoglutein occur in the region where antibody binds. so we do essentially this evolutionary dance. we make antibodies to the hog. the virus changes its composition. and that's why we have to continually reinvent vaccines and keep up with this tremendous diversity that virus poses to our immune system. now, tony mentioned this particular slide. there have now been a number of laboratories, this particular one from description, there's another one from harvard medical

school and others that have actually been around for a number of years -- from scripps. we're now beginning to recognize these antibodies shown here at the base of the receptor structure, don't -- don't play with the highly-variable region of the receptor. they go at a much more conserved and fundamental part of the receptor hemoglutein. it's part of the structures that's required in rearrangement and fusion of the virus to its target cell. so essentially what we now know is where all of the variation normally occurs in this receptor-binding domain of the hemoglutein. that there's another portion of the molecule that in fact is a hot spot for these broadly-neutralizing stem antibodies. what i've done is to map onto the trimer the context for these broadly neutralizing antibodies. why is this important? had we a vaccine like this available when the 2009 virus

came along, i'm now shoring the genetic variation of 2009 virus among all of the h 1 strains that have been encountered. and you can see that region 2009 is highly vulnerable and can be neutralized by these antibodies to the stem. and so obviously an universalñi vaccine directed at this target would have worked for 2009. and we're pursuing a variety of different approaches in the laboratory to elicit these antibodies. they involve priming and boosting. priming with d.n.a. plasmas as you've heard. in some cases boosting with the conventional vaccine. in other instances using the priming and boosting vectored approach that is i showed you earlier in the talk. so in summary what i've told you today is that we have generated experimental vaccines that protect against previous lethal pandemics, specifically the 1918 spanish influenza.

that obviously could give us a measure of protection against this virus should it return, a or it could give us protection against related viruses in the 2009 in fact does have some similarities in parts of the viral hemoglutein. your understanding of influenza structure immunity are providing opportunities to develop vaccines preemptively, for instance adapttation against the -- or evolving forms of the 2009 h1n1 influenza virus. that's another area which we need to watch very carefully. and finally this understanding of structure and genetics and the sites of neutralizing antibody interaction is essentially to vaccine design for universal flu. these are efforts now moving forward in their very early stages with different gene-based or vector approaches to either the hog, the nuclear protein or

n 2. thanks. -- the hemoglutein, the nuclear protein or n 2. thank you, dr. nabel. to those of you viewing on the web, if there are any questions you'd like to send in our e-mail address is hhs studio at hhs.gov. feel free to send those questions in and we will take those at the first opportunity we have. our next speaker is dr. carol heilman, director of the division of microbiology and infectious diseases at the national institute of infection us diseases. >> good morning, everybody. it's a pleasure to be here and give you an idea what's been going on in the extra mural program with respect to the development of new influenza viruses. so i'd like to first begin by giving you an orientation to what our mission is within the

extra mural program. briefly we are supposed to be and we are responsible for a lot of the basic research that does occur in the influenza. but this basic research is really guided towards the development of new therapeutic, vaccines and diagnostics. in order to go about and do that we also need in our armament a lot of research resources. this will help us december into those end products. and we also have an opportunity to do a lot of field and clinical testing. the major goal of this program is to essentially discover and lower the risk with respect to the ideas that are behind new vaccines and new other product technologies. also to give you a perspective -- and i'm sorry this is difficult to see. but extra mural program is about 93% of the extra mural program is devoted towards influenza virus with respect to the amount of money that we spend on influenza virus. and this again is a yearly look

at what we spend on influenza. 268.1 million in fy 08 of which again 93% of it went to the extra mural program. within the naid, the way we divide these funds essentially are shown here. and again, a vast majority of the efforts are focused in on development of new influenza virus vaccine. so again, just a reminder of what it does take to get to a vaccine, it's important and i know robin will be going into this in more detail, but in addition to having the basic research and the ideas behind what we would like to have in terms of develop new ideas, we have to test these new ideas in a very rigorous matter in a lot of animal model systems, in a lot of in vitro systems, a lot of safety issues in a preclinical setting before we can even get to phase one. and the naid really concentrates a lot of their efforts in this

particular area but that does not mean that we have not particular areas when we have indeed needed. to and also a lot of the process development that you see at the end point came from a lot of the basic research and ideas that have started out in the beginning. so in order to actually execute a lot of our ideas, we also have a system in place and this is one example of many systems we have in place which is called our vaccine and treatment evaluation units. these units again have been in place for a very long time. these units are housed in academic centers. and this is the current group of awardees that have those awards. and they have been involved over the years for many, many phase one, two and three clinical trials. their focus has been on any particular vaccines, for any particular pathogens. but to be quite honest with you, a lot of their efforts have gone towards development of influenza

vaccines. so we spent some time this morning give you can an idea of the types of technology that are out there. i'm not going to spend time on giving you an idea of what is going on in these two areas because these are licensed vaccines. but i do want to tell you that there are still investigators that are trying to make these two ideas better. for example, in the live attenuated vaccines they're trying to incorporate some of that maracaibo proteins into the backbone of the virus to find out whether we can get even broader immune response. there are activities going on here but i'm not going to focus in on them. the gary presented a lot of what is going on in d.n.a. vaccines. i want to talk a little bit more about what we are doing. the way i've tried to organize this is because we have at any point in time between 50 to 60 investigators going into the depths, very similar to what gary has said, i'm trying to give you an idea about what is

going on in the general area and then i'm going to try to give you a few specific examples. but there are in each of the areas that i'm going to be presenting, threw three areas of emphasis. one is the groups are trying to identify the best antigen combination. in the case for example of d.n.a. vaccines, gary has mentioned that there's efforts going on about m, marabout n 2, np. there are also efforts going on again as gary has mentioned about the small little areas in the ha. so whether or not you're looking for a common epetopes, for example things within ha's common across, or whether you're looking to either separately or in combination put them in with the marabout, m 2, np, there's a lot of efforts trying to figure out what is the best combination for the antigen that we'd like to do. there are also efforts in terms of trying to figure out how to

increase the immune response. so in this particular d.n.a. segment that you have, people are modifying it. they're putting in other genes that may target or elicit a more broader immune responses. they're putting in genes for reaccept tors that will target them to certain tissue. there's a lot of little genetic engineering that is going on there with the whole goal of increasing immune response. and with respect to the second area, optimizing delivery methods, again this is going on very broadly in all the technologies that you're going to be hearing about. but in this case, there's for example people that are looking at new deliveries such as gene guns. but there's also people for example that are putting these d.n.a. segments into somethingñi that's called bacterial ghosts. they're essentially just the membrane of the bacteria. and the reason that they do that is twofold. for example, you can use salmonella as a ghost.

you could put the d.n.a. in there. you could swallow the d.n.a. the d.n.a., because it has the salmonella proteins, will go to your lymph tissue within your gut, it will be ingest by the cells in the lymph system and it's a wonderful delivery system directly to the targets that you want it to go to. the other thing that people are doing in all the systems i'm going to be talking about are optimizing manufacturing procedures. for example, how can i get this particular segment to grow as rapid as i can get it to grow or to be as effective when it gets into the cell? in this particular case that's the kind of manufacturing procedure. how can i get the cells to manufacture that particular d.n.a. sequence rapidly? so next concept that i'd like to spend just a little bit of time on is recombitant substantial vaccine. most of the focus seems to be

going on in optimizing expression systems. and what i mean by that is tony has explained that what you simply do over here is you use this kind of technology to get protein of whatever sort that you would like. but one of the things that we do know is depending upon how that protein comes out, it can be looked at by your immune system in different ways. so people are looking about how to get the optimal confirmation. do i want rosetta formations. i do want a different type of globular head? what do i really want this protein to look like in the end? there's a lot of effort also going in on yields. so exactly what vector you choose to use, will help in terms of what your yield is going to look like. and this as again has been mentioned before is one of the most advanced technologies. so i just want to give you an example of why this technology is where it is right now. and what the potential of it is

in the future. again, this is an example of the virus expression system that's been done by novavax. in a phase three trial, under bla at the f.d.a. but the value of this has been you are able to identify right away from this sequence what it is your ha gene is that you want. and you could immediately put it into, in this case, a virusçó tt infect insect cells. the value of that, once you've gotten it in there, again early identification, you get it into your vector, you put it into your cells, and within 48 to 72 hours that's all it takes for it toñr grow. the yield of this, once you've gotten it to grow, is about 90% of the final product is what you're looking for, is that prow teen what you're looking for so you have a very effective vehicle for getting very effective yields. and finally, just to give you an

idea, this particular firmenter at this size is the equivalent of 50,000 eggs. so again it's a very highly-efficiencies term that they have here. let me spend just a little time now on virus-like particles. and again as tony has shown you, this is like a ghost cell here. again, there's no d.n.a. in here but you use it as a delivery vehicle. .

vrn salmonel >> again, this is if situation where you have a virus. something that really doesn't cause you problems and you pepper the cell wall with different kinds of proteins you're looking for. the focus of this area of investigation is which one do i want to use.

example. an energies and corona viruses and if i can actually have a vector that not only delivers influenza but other a then agains maybe you can have a really universal pathogens and viruses. so there's a lot of areas of efforts going on over here about which exact vectors to use and what are the values and particular proteins should be inserted in this to max nice immune response that i'm looking for. and finally in synthetic peptide vaccines. in this area, this has been an area again just to remind you where you can literally synthesize amino acids into whatever peptide you want. are there ways to enhance this particular ability of peptides

that haven't in the past been very i tune genic. they cog gi gate and certain receptors go right to the sells i want them to go to. i told you about that ghost if they take the same and put them on the end they can traffic right to the lymph tissue i'm looking for. and whether or not i can pieces of molecular adjacents to this. this is efforts on-going there with where are we in this whole system. the big examples show you that most of the work in all of these areas are in basic research or pre clinical development. for dna we have one company that has gotten they're product into a phase one trial. for recognizants we have one that's gone through three trials

for virus like particulars. we have, this is right. this is protein sciences. i'm sorry, virus like particles is nova max that's had put their products in stage two. we have two companies that are able to get their products to and we have not funded america but i bring them up we're not the only people doing this. lot of companies are actively involved but, m erk is looking for synthetic peptides and has gotten them with phase one trials. i'll end with reminding you, we really are a at the beginning. we're seeing the end point now is reflective of efforts in on-going for 15-20 years so this is not a new idea for us.

these 50 or 60 projects are not new for us but they have indeed pushed a lot of activities of this particular set of stuff and i will end for this and then we can go on to questions. thank you very much. >> thank you very much. at this point let's take a because and see if there's questions from any of our speakers that we've heard from so far? yes? go ahead. press the button and identify yourself. >> two questions. one for doctor patchy. could you ran it can five platforms in terms of the readiness for primetime and for doctor noble. once we produce vaccines for the stem proteins want that same process happen that's happening to the receptor binding region? >> well on to your first

question, actually, doctor helmin showed the stage. specifically to a dress the question it's the recome by nance sub unit vaccine where you take the and gene and insert that and infect in vitro insect cells and then you have the protein coming out. that's in phase three and is the process of interacting with the fda to try and did he recall what needs to be done next for licensing. >> in terms of the stem antibody that's great question, in fact, i think that at least among theh 1 viruses, that's part of the virus that's fundamentally what we call functionally required part of the virus. we think it's going to be really

hard to knew tate away with simple mutations. having said that it would not surprise me if we haven't seen some of that evolution in a different way over the years with flu and that is when i showed you the picture of the,h 3 verses the,h 1. that stem region is actually very different from the stem region in,h 1. so i think probably what's happening over the years is viruses have developed new subtypes in part to get away from the pre-existing in immunity. the end game would be to have a cocktail of antistem antibodies that essentially would constrain the virus from even switch together new subtypes and i think in the meantime we could be pretty effective in a subtype at eliminating that particular strain.

>> i - any other questions. i had one for doctor helmin i wasn't quite clear on. the vector based platform. where you said one potential path of development was the possibility of developing vaccine that might be targeted against multiple rest spir or the diseases besides influenza. could you elaborate? >> that's correct. again, if you're thinking about other viruses like parn flu this is also a virus that causes especially in young children. relative levels of severe morbidity. so if you can construct those that you still want on the surface proteins and other influenza proteins expressed the possibility of your antibody responses being much broader is really what the goal is right now. it's still under investigation

but that would be an end goal. >> okay. any other questions at this point? again, if you have any questions for the viewers on-line, our address is,hhs studio at dotg ov. i think we'll continue on. at this point i'd like to have robin robertson come up. director of the biomedical advance medical facility and talk to us about eggs, cells and beyond.

>> past present and where we'll be ten to fifteen years from now. introduce you to one of the new kids on the block so to speak. pandemic has a prepare edness biomedical advance redevelopment research. barta where we're providing medical counter measures for chemical nuclear threats and emerging infectious diseases and we've moved a long way with pandemics and we'll be starting soon with emergency infectious disease. this could be in the form of vaccines and even ventilators and other nonpharmaceutical products. where we were in the u.s. government to provide these products, as you see, we're right here. we take an and off for the,nih and some of the department of

defense and early and research and early development. we do advance development and we do acquisition and stockpiling and work with our partners at,cvc on the storage and maintenance of that and work with them to make sure it's deployed and utilized. fda has oversight of all of this. we have the defense science board that offers an overlook of decisions going forward. this is all part of the public health counter measure enterprise which is a governing body within the department and within the u.s. government for counter measure development. as pointed out earlier, this is a long continuum for development. this pipeline we see many products that candidates have to be invented basically. and then they have to go through so you actually get one or two at the end. where we work with partners

atnih and department of defense. once products move out of phase one there's an and off there. there's a dotted line because as carole pointed out,nih works past this and in some instances we go earlier. but we have a very fine transition there. that actual baton and off of these product bus you see new jersey order to have something at the end we have to have many products going forward. i bring that to you because, as doctor faucher point out. the shortage of vaccine in 2004. the reemerging of the,h 5n 1 avian and the katrina hurricane response led to a real need for national strategy for pandemic influenza announced in 2005. implementation plan came out in 2006 relative to that, for

influenza vaccines was ability to have for the country at some point, the surge capacity to produce a large number of vaccines in a very short period of time for everyone and have pre pandemic vaccines so we set up an approach, this is basically about 2005-2006 for pandemic flu and we basically very for vaccines had advanced development. stockpiling and inquisitions and restructuring and rebuilding. i concentrate a lot on the vaccines moving forward with some of the technologies that are now right for coming of age to actually be to the market and actually used the coming years. also, with the stockpiling our efforts with,h 5n 1 and h1n1. an effort is how can we build

domestic manufacturing infrastructure with egg based supply or retro-fitting those facilitys and the new cell based manufacturing facilities and new recumbent manufacturing facilities. sub-base influentialed vaccines of course has been said before, provided more robust scaleable vaccine platform leading to manufacturing problems as we saw this year. the virus not being able to grow very well. we've awarded six contracts since 2005 at the cost of 1 point 3 billion. we had many candidates going forward so we would have several that would actually make it to the market so we had certain requirements for them. not only for them to develop pandemic vaccines but seasonal for manufacturing and search

capacity. 100 million in six months. that's commitment they have to make and hurdle they have to jump. those contracts went to many places, where are we now? two have completed phase three clinical studies so they're very far along and we expect them to submit license together the fda in the coming year. you there two manufacturers are in early stage development and as we planned and expected. two have been down selected 2009 because of business reasons they did not want to go forward with products or could not show it was super you to egg based. that's where we are again instead of eggs you're going to see these large 2-story bio reactors where you have the virus growing. that's a closed system as pointed out so. it actually has less vulnerability to micro somes.

not only can the facilities make influenza vaccines but in an emergency they could make others as well. as pointed out there's other types of vaccine technologies that can boost the immune response anding a tants these stimulating molecules can provide dose age effects so that maybe one dose you may be able to get four, maybe eight doses out of a given amount of vaccine antigen and they can provide cross strength protection and enhance immunity so we've awarded three contracts in 2007. cost of 133 million. many of you know many of these products. also another type of vaccine and another delivery system for trans dermal delivery where you actually put a patch right on top where you add minister the vaccine and that activent would

come in and give a stum lating effect there. those studies are actually in phase two and a this year we awarded three contracts for further development of theing a vabts with h1n1. so as we go forward, those are the now four different companies. pastor. two of the manufactures probably would have submitted license with,h 5n 1 vaccine with the,ing a vents. had it not been for the one pandemic. the other two are in early development. before in phase two clinical trials and the fund doesn't see

where those go. the third area of influenza vaccines are technologies and this is would allow us to be less dependent on the influenza strain properties including the ability to grow. you only need the influence of those known very early and should be able then to be inserted into a vector or into one of the other technologies and be available much sooner. this is an example of one of those vaccines. flu block from protein sciences we awarded a contract to them this year and in june for total of 15.25% million over five years. they're laced with seasonal. have an h1n1 vaccine they're producing. what has brought them up to this point? that's this industrialization and scale of development of the

process and then any late stage clinical development or post licensing. how we actually get it from the lab bench to commercial scale production is what we're working with. their committee meants to officially have to demonstrate they can produce 50 million doses in 6 months and that their initial loss of the vaccine can be done within 12 weeks of a pandemic onset. doing forward we have an, rfp or solicitation for proposed in september. we've received a number of companies including that we will award early 2010. contracts for advanced development of these products. have been talked about earlier. we have anh 5n 1 bug stockpile. that virus is smolders out there. we have protection in that form

and wanted to have enough for the critical workforce and what we see, weing an advantages to that we can have a 125 or more vaccine right now for that. our vaccine manufacturer and building provides eggs, from egg forms and certain parts of the country to these actually these, stockpiled vaccine. to actually building new facilities. this is the one in north carolina. you see the still was there and recently a couple of weeks ago we went to the grand opening of this facility that will become operation to make vaccine for americans in 2011. this was part of a five-year-plan in 2006. as we go forward we'll award more contracts to build more domestic manufacturers. whether cell based or recouple

by innocent. how did all this come to bear? in 2009 h1n1 pandemic the,nih and we worked on the clinical development of these vaccines and worked with the manufacturer to get the development product to them and supported manufacturers in doing they're clinical trials. responsible for having the vaccine and producing raw ingredients. both vaccines have a fill finish anding an aggi vents and continued to work forward to get that vaccine distributed oversee the administration with state and local governments. so stochl products that have come to bear. h 1h 5, h1n1. spray and other products are

licensed product with the my flu and experimental antiviral drug. used under emergency use authorize in critical ill individuals and has gone to over a thousand and helps reduce the more billty with that disease. where you can find this? the we. okay. >> thank you doctor robinson. any questions at this point. gretchen we have someone on-line. >> i have a question, actually i don't think this is for robin. probably for either doctor able in or hidele man with the canadian press. her question is regarding new platforms sit anticipated at all that most of these is needing to

be used with, aggi vents and do purified proteins produce that to the current vaccine? >> aning a vent will have something be a response. whether or not alone will require ago i vent is a question for further in the clinical trials. as you saw from çócarole's flow sheet we're at various levels with these. i would not be surprised that you, in fact i think you eluded to it carole. some of the proteins out of the reincumbent system you will in fact get a pretty good boost with an aggi vent. and the pro teents we get when we do a regular killed or

activated vaccine. conceivably yes but it's case-by-case. >> it's not something that possibly wouldn't be recorporated in the future but i think theing a vent is really just an additional tool that allows us once we have a lead to see if we can dose spare as robin talked about or to make it more effective and at the moment, i don't think it's a requirement. in terms of whether the recouple by innocent proteins are as potent as existing vaccines i would say it's early days. in general, they probably are not quite as potent.

one of the reasons for that is that if you look at the flu virus there are about 450 viral spikes on every virus, so it presents those proteins in a very concentrated focused way. just the same as they are on the virus. when we give purified reincumbent proteins they're not at the timered at least the first generation is not in the same way and really aren't at the same absolute concentration. so that's one reason why aggi vents are being looked at. my pro diction is as the production gets better and as we learn how to better manipulate the proteins scientists will start doing the same thing, and i presume that the efficacy will improve overtime. >> yeah, and i'd like to for a few exacts of what he said. people are thinking right now

about trying figure out how to best present it. people are putting proteins into like nano particles. doesn't have to have an, aggi vent associated with it. if you think of a polymer delivery system there's ways people look to present the antigens in that kind of way and that is other ways it's thinking a side froming a vent. go ahead. >> the companies s say markets are uncertain there's a high utilization of seasonal vaccine in the united states are those

things that you might address? >> well certainly you point out a problem that, what's the sustainability of all the efforts we go forward within being able to have all the new companies and products there. part of that is what bruce is worried about every day and that's, how can we have more people take influenza vaccines on a year to year basis? not only with the companies but the government how we can encourage that. i think we have an opportunity now with the 2009 h1n1 pandemic to really educate and bring out the outstanding qualities of that type or more people being vak nighted. part of what we've done though is actually helped manufacturers get the return on their investments sooner by helping them with advanced development. and so they receive contracts

that are very large amounts and that's money they don't have to spend and they can actually go forward and spend it on something else. it takes about $800 million to a billion to move a vaccine product from the beginning. this is carole talked about, to actually having it on the market. again there the other places we have to call sharing on the building of this facility is part of the way we're helping them. >> just expand on that a bit in the mind of i'm sure all of my colleges the best way to get the stability to the system where the companies have a degree of confidence that things not going to roller coaster on them is to get more and more people vaccinated each year. influenza over the last several years with increase and expansion of the recommendations from the cdc. we've gone from 50 million up to now over 100 million. as a public health person, i would think that the goal that i

would see to really stabilize theñlsystem and therefore make t less of a crisis issue when you get to have a pandemic flu which we know will again occur as was predicted even though they're rare they do occur is to get as many people vaccinated as possible. and what we foresee in the future is influenza vaccine will be a routine vaccination for everyone. if we then transition that into the universal vaccine you may only have to do that every couple of years and get people protected not only from seasonal flu but pandemic. in my mind, that's end game and that's good for the companies because they know and pre direct the vast majority of the population will get vak nighted not having to guess. the thing in our favor is if track record is extraordinarily

good regarding safety and clearly they're effective. we have two big pluss in our favor for that. >> and you said, building on this for everyone. we focus on the u.s. market and what's happening but clearly as we've all been reminded with all the discussion about pandemic this is not just a u.s. problem. companies are looking to markets as well. it's a driving principal of the pandemic preparedness to do what it to increase seasonal vaccine to have a larger base of capacity on which to build. it's hard to start where you are to have instant surge to handle the global problems but more seasonal use not just in the united states but around the world the more this based to build on. >> to follow up on what he said. once we get to to holy grail of universal vaccine won't that put the other companies that spent

the billions on the side roads out of business? some of the other things you've been speaking about? >> i'm not so sureñlit's going to put them out of business but i think if you do develop a universal vaccine there are many, many, vaccine preventable diseases that we still can make vaccines about and if you show the company west have a stable market. we'll not stop with influenza. the subject of the subject so day is influenza but there's a few other diseases we'd like to get things. tu burr cue low sis and ma ler you just to name a few and aids. >> broader context of universal just to project how it would happen and i think, it's important to realize it won't happen overnight. fda wants to get a good look.

we will too at how effective and safe they are i would say that even in the best case scenario if we had a candidate to go forward in the next five years there will be some interim where we still use the seasonal vaccine at the same time we move in some of the universals into play. plenty of opportunity for the companies to adjust to the>> ledge base to the new products and to again do the things that tony described. >> question from on-line? >> yeah, we have a question from marion from yuan rersty of minnesota for doctor robinson. there's been vocal opposition to the h1n1 saying it's untested and now. when it was based obstacle along established vaccine. given that how are you planning to persuade the public to truly accept a new flue vaccine with

new technology? >> well i'll start. i think there's nothing special about flu and new technologies. i think what we've indicated is there's a number of new technologies coming that trajectory and each time-line you've seen are quite long. there's a lot of ideas that have to go with many stages with increasing experience. there's a whole series of tests to can he remem determine how s. it's able to demonstrate the science base for why it's been licensed and recommended. some may hesitate until there's more of a track record. i think that's true with every product. but i think it's our jobs to demonstrate why it is the vaccine has achieved the status to be licensed and recommends and some may want to wait longer than others but particularly when the diseases that the vaccines are preventing are very

clear, then i think people have a better understanding what the value is of preventing that illness. >> any other questions before we move on? okay. i think we'll move on with the final two speakers. critical partner the food and drug administration. regulatory processes to this whole endeavor so. our first speaker doctor jesse good man the chief scientist and deputy commissioner at fda. thanks. >> excuse me. well, i'm delighted to be here. thank you for sponsoring this event and i'm happy to talk about how we're work together apply regulatory science both to increase the availability of current vaccines and then future vaccines and i think safely is really important bottom line here and is part of the answer

to the last question. now as you can see here, we're trying speed theñr things up. this is for people who live in the district of colombia. this the kind of speeding ticket we prevently get but we want to speed things up without causing problems or safety issues. we've heard a lot about curves and bending curves and i wanted to have a little time but i didn't prepare a slide. i think what we're really trying to do here with influenza vaccine is in fact, there's a curve as the pandemic occurs there's a lag to produce a new sb vaccine and this is true with seasonal so this period of right now almost about five months where before going very, very quickly we can begin to have any vaccine. that's where the curve is flat and then it goes up and then that goes up. and i think what we want to do is two things.

shift the curve to the left so that we get vaccine sooner and faster and those are really transformative technologies, some of which we heard about. we also can increase the slope of the curve so we get more vaccine more quickly. so both of those things can happen here. i want to say a word about regulatory science because i think that something you've heard in some of the remarks here is that we really play an important role for the public and we're commonly perceived as being sure these products are safe. but we're also particularly with vaccines engage that every step of the way. here, in trying to get something that is a concept or works in an animal to become a reality in a product that can help people. as noted here there's a large gap between some of the amazing

advances in basic science where we can understand something like glue on the proteins in a single atomic kind of level, and the availability of a final manufactured prohibit. in fact that it's at it's most extreme has been called a valley of death gap. there's a lot of reasons this exists. one is because it's quite hard to go from that concept to a product that can be reliable and reproduced or manufactured. another is that a person is not a mouse. there's lots of experiences with things that a drug or vaccine works in an animal system and, if it doesn't work in an animal system it's very unlikely it will in human. just because it does doesn't mean it will. so one of the things we try to address c this lack of information and tools to get from that idea to a treatment that might work in a mouse but

something that can work for patients. this is not a problem unique to vaccines. cancer therapys in area of very intense investigations this is commonly a problem. so we believe that applies regulatory science which is frequently in collaboration with our colleagues at nhh can help bridge the gap and get the products there. also in this evaluation process we do can take innovative steps to make that go faster as products are developed. one of the things we really put our resources into, is when there's a very important public health problem like pandemic influenza to interact intensively with the product developers from the earlier stages and try to say, how is there a process of production and evaluation, et cetera, we discover problems or we speed it up early rather than coming to a point at the end of the day

where let's say a product can't be manufactured or there's a safety question late in the game. we try where possible to provide guidance and example, i'll mention, we've provided guidance on how safely to produce cell culture vaccines that all manufacturers can use to accelerate development and then we have regulatory mechanisms including accelerated approval. accelerated approval allows us to approve a medical product based on what we call a likely surrogate marker or something that, short of preventing the disease is correlated with a high likelihood of preventing the disease. and example with influenza vaccines we know the antibody response against the he mo' glob in is a reasonable measure that correlated with protection, it's not perfect but this is actually allowed us in the last five years to approve four additional

seasonal vaccines. one to two years or more earlier than they would have been approved and even though we all face the supply challenges, with seasonal vaccine and this year with the pandemic, we're much better off because of a broader spectrum of products we have to choose from. now i think most important where fda can help is working on science to get tools and standards that improve our evaluation, or improve the speed and quality of testing and manufacturing of vaccines as well as evaluation of their safety after they're approval. i want to say that this is a major priority of our leadership at fda right now. is to strengthen the agency as a scientific agency and to make us more able to collaborate and have more capacity to really facilitate product development. in our focus areas here, it's

all critical for our response to influenza and other public health emergencies. this includes development of novel technologies. probleming for unmet public health needs. how to incentivize where the markets are not as strong as for some therapies and part of the way to incentivize this is helping in the regulatory science process and harnessing the information and genome, et cetera. one thing people don't realize but we live every year and this gets to what can we do even with what we have now, to improve how quickly we mobilize vaccine, is that influenza vaccine it's almost as if we're preparing for pandemic every year. there's new viruses that emerge and based on that surveillance

we pick new strains of virus and uniquely here, fda in particular, our center for biologicals. in a minute you'll hear about this but fda is engaged with the global public health community, with cdc and manufacturers in being sure we get a vak sin each and every year. it's much accelerated this year in time and urgency. but many of these places there are really opportunities for improvement so you've heard about how egg based vaccines are 50 plus years old and we need additional technologies, the same is true for many aspects of how we evaluate the vaccine each year and release it. there's room for improvement in those areas and imimprovements we make will benefit us with

cell culture vaccines as well. we've, with support from,shs and congress we've put efforts into improving how to do things and get vaccine out each year. these are some examples of where we're engaged. so for example, every single year we work with colleagues around the world to select the strains. quite honestly, we can use information sciences and molecular biology to improve how we do that and we're engaged that in that. we work with global network of laboratories and cdc and others to help produce and then characterize what we call rea sorting. we take this wild type virus we grow from people and transform it into something that's safe and suitable for most manufacturing processes. but as occurred this year and occurs not in frequently with

see some seasonal vaccine. some eggs don't grow well in some. some strains will not grow that well in certain cell cultures either. so we're working on methods to improve growth in manufacturing. we have so get create reagents to measure the potency of the vaccines we then produce so human beings get the right dose at the doctor. this current method are probably more archaic than actually egg based vaccine production itself. they rely on methods when i was a medical student were a curiosity then, and certainly are now and again we're working on methods to measure potency that don't depend on having commercial vaccines available. today's methods before we can

really use them. the vaccine itself has to be available. this is a matter of taking months that should be able to be reduced to weeks and doctor we're will talk about some of those efforts as part of our quality and safety oversight, every vaccine is carefully tested and exampled. the methodologys for doing that are in many cases, poised for speeding and improvement and including uses using rapid methods to detect like my tone you contamination. samples from clinical studies like we used this year and doctor fauchy and also industry performed in record time studies to show this vaccine had an excellent immune response. but we measured that exactly as it was measured also some tyke

like 40 years ago. we need to improve that and need to improve how those measurements correlate with what then happens in the patient. you'll hear a little bit about that. and i don't want to leave out safety assessment and monitoring. even once a vaccine is approved and tested and distributed even though we have very high safety expectations and our regulatory requirements are rigorous. we know that very rare adverse events can always occur and we know that products being given to millions of people have to meet a very high safety standard so. building good surveillance systems that use healthcare data to detect unexpected effects is extremely important and i'll get to that. now in a pandemic as i mentioned this becomes compressed but there's also unique needs and global coordination and we with our colleagues at,w ho have led

an effort to bring regulatory agencies around the world to share information and try and get vaccines developed not just for the united states but for the world more quickly but you know the real issue there, if we think in this country we have a challenge in terms of manufacturing capacity and seasonal immunization to prevent flu, the world has a much greater challenge. we're well off compared to the world and in fact, our response to the h1n1 pandemic has been very rapid compared to what much of the world has been able to amount as is our capacity. and again, obviously in these situations as you've seen. we can turn around and rebuke things as is mere itted by the public health emergency. rapidly we can potentially if the secretary of,h-hs

determineed a public emergency and we don't have licensed products that meet the need we have emergency use authorization that can allow us to even consider unlicensed products but to do so based on the assessment of the sciences in terms of risk and benefit for. example doctor fauchy mentioned vaccines which we have, the ones that could have been used the united states this year, are not licensed products, however we've been collecting data on those and if they were to be needed, this is the kind of pathway we have available that even prior to lie sen sure we could evaluate them. then we've done a lot working closely with barda and manufacturers. people don't realize once you produce the vaccine and certainly the biggest factor in the gap between su blind demand this year has been the slow growth of the virus.

it just didn't want to behave and every time a manufacture thought they improved the growth it didn't behave again. that's biggest factor but there's also getting that bacterial vaccine into viles once you've grown it and we've tried to come press that by bringing on additional capacity. i want to end up talking about the new technologies and what are some of the issues that people may not be thinking about that make these not so simple. there are incredibly promising things here and think along with the other speakers that we're poised for a transformation in how we produce and use influenza vaccine. we're going to have more capacity and methods that allow us to increase reliability and speed of production, but again, getting going from the mouths or the human clinical trials to

large scale manufacturing and a suring we do that safely, is not always a simple issue. now you've heard about a bit about potent novel agivents. these include oil and water agivents available right now. one has been in a european licensed flu vaccine used only in the elderly but for several years in europe. we recently improved a human pap low ma virus or cervical cancer virus including a noveling a vent. not exactly the same though. we're quite interesting as doctor fauchy mentioned they offer the potential to increase the immune response with h 5. we could not produce an immunele response without adding a,ing a

vent. our studies said we could have a robust immune response without adding, agivent responses. but they do response increasing yield and an amount of vaccine available potentially improving seasonal vaccination as well. if example. children and elderly might have a stronger e immune response. we're really looking at these. there are potential issues. these do cause an inflammatory response. individuals who get these have sore arms and when they have a sore arm, it's sore, they have more fever, et cetera. when considering a serious disease like influenza, those may be kind of effects that are expected and not of the degree that me right particular concern. however they do indicate there's

a biological response going on. there's no evidence, but there's been concern that could these stimulate unhelpful immune responses against, antigens of the body or autoimmunity? there's no evidence of this to date in humans but we need a better understanding how the agivents work. could we, example, separate the boosting the immune response against what we want to boost it for from causing these more general inflammatory effects? this is a great area for basic science. we don't have time to mention it today, but we have people looking at what are the, can we get better tests for safety using, for e example the response of human cells to an agivent to predict what a response of a person is going to be?

as you heard from doctor robinson. hhs has been sponsoring and we've been very involved also in getting more data about these vaccines and as you heard, we do anticipate the potential that some of these maybe submitted to the united states for licensing in the near future. now so cell culture vaccines. i think it's important on background again to say, these will not transform influenza vaccine production but they could be a great help. they could increase reliability in some cases, viruses may grow better. and as tony mentioned, they could increase our ability to scale up quickly. potentially. and it's important for the public to realize that there's nothing new or scary or novel about cell culture vaccines. we've been using them for years.

almost every viral vaccine currently available. mumps, measles. et cetera. polio. one of the greatest vaccine success stories of all, are made in cells but there are special is a challenges of sells and the reason we don't have the cell culture influenza vaccine is not because of some major safety concern, it's because it's taken a long time to get a good yield and a good antigen out of cell cultured influenza vaccines. another case where the flu virus has not behaved in the way we would like it to. this has required looking at new cell lines. new approaches to creating cell culture vaccine and very recently there was a first cell cultured influenza vaccine approved in europe but like the agivent it's important to

realize in responding to the 2009hn 1n pandemic the first vaccines available were egg based vaccines and nonagivents. so even though we're beginning and i think, as i said, the vaccine programs will be transformed by things like cell culture vaccine. we're in a transitional period between how we've done it historically and how we can do it in the future. again, many licensed vaccines but when you use a cell, there are some important safety concerns that you need to address, and an important point, is you can very successfully address them if you do this properly and this is or an area where regulatory science can help. a cell can carry along, not just the virus you want but potentially other viruses that could have been there to begin with when that cell culture line

was made or could get in there somehow. and - some cell lines, most do not, but there's some that because cell lines often maintain the potential to proliferate that in theory, could have genes or other abilities to cause tumors so it's very important to make sure the vaccine you produce in a cell line like that is very pure and doesn't have any of those properties. this can be done and it can be done relatively easy and in fact, cell culture vaccines now are among the purist vaccines that are pro accused and again, this is because of high fda standards, testing extensively. in - we heard this recently in the discussion of one of the recumbent influenza vaccines which as you heard, made tremendous progress but it too

has grown in cells and insect cells and it's very important to, you could potentially have proteins or residuals that could cause allergic or immune reactions. this is why cell culture vaccines are highly purified to prevent that problem. now fda has had an extensive program to try and design and share with people guidance about how to make these vaccines pure and safe, how to test for what we call infectious agents to make sure they're not that there. fda has an essay called the part called retro virus in vaccines and in fact, we've had tremendous support in a partnership with doctor fauchy and national sut institute of infectious disease and we see these vaccines coming along

safely very much in the near future. you heard about recumbent proteins and virus like particles and again, there's - we're not a ler dpik to those. they just need to be produced properly. there are approved vaccines that are recumbent such as hepatitisb that's saving millions of lives around the world. cervical cancer vaccines are virus like particles. this is technology where we're gaining experience and there's no reason it cannot succeed for influenza as well. but the problems here are very much in, how do you make lots of it? how does the protein come out the same way every time? because these become very complex systems and the consistency of knowing that an influenza vaccine in january and march is the same and is just as safe and effective is critically

important. and then we did hear about novel targets and universal vaccines and u think it's very important to emphasize as everyone has these are several years off. if we can succeed. because this is a very genetically variable virus, influenza that has tricked humans time and time again. there's a reason it caused global pandemic. very similar to a different infectious disease. hiv but it presents similar challenges in that, it is a virus that changes itself, not just annually but daily. daily this virus is changing. the biggest challenge here from an fda evaluation and scientific point of view is that, the real way we're going to know these vaccines protect people is seeing that they protect people

and that's going to require real clinical day day. we don't have antibody datas against hemoglobin that tell us that it will be protective. whole science needs to be developed around these vaccines that tells us what's protective. and then just a close again, very important. that these products be safe. as i mentioned earlier they're given to millions of people. they include children and track record of safety has been extraordinary. we're monitoring the h1n1 this year and that track record is as expected but we're monitoring it continually positive. we're building systems now that enhance our safety surveillance and a built to detect any unpredicted problems more quickly and i think we also can harness modern biology. there's people with rare,

serious adverse events to any medical product including vaccines and we can start understanding what it is about those people and they're genomes thanks to the human genome product. .

the efforts to provide regulatory science to support that transformation. thank you. [whispering] >> thank you.

thank you to everyone for hanging around to the end. my goal is to be brief and provide you with a short update on the research at the center for biologics that supports the influence of vaccine availability. we have a somewhat unique role regarding the vaccine production and development. do not only to the uniqueness of influenza and the fact that there is a new vaccine every year, but also the public health importance of the virus and the disease. i wanted to give you a snapshot in the support of the production of influenza vaccines and the facilitation of the development of new ones.

we also developed seasonal influenza vaccines. these are interrelated. you prepare for one by being prepared for the other. it is our job to look down the road and be prepared. you heard the second part of the slide showing the challenges that we face. i wanted to give you a quick snapshot of hell hole we were

hoping -- how we work. we have to standardize those because they're made by different manufacturers. we are increasing sensitivity of the entire process. four new vaccines we have to define protections. many of the new vaccines will not work the same way that traditional ones have worked. we will require new methods for products and considerations. i am going through the next snapshot. the challenges for improved vaccine production, if you think about it the total amount of vaccine that one can produce is limited by the poorest growing

virus strain in the mixture. every year that is influenza b. there is not a high growth assortment available to make that a high producing strain. some of the recent work we have done to address this problem is shown on this slide. this is important. it is not easy to develop high growth in the way that it is for influenza a. on the other hand we have reason results that show that the amino acid changes can influenced by richfield's. -- virus shields. one single amino acid can change in the a molecule to result in a

tenfold increase in virus yield. there is a fourfold increase in total ha content. interestingly, the adaptation correlates with receptive properties. look at the color coding on the right. it shows the original low growth of the virus. the green line's showed the black hands of our tobacco for infecting sales -- cells. -- typical for infecting cells. there is a possibility for improvement in influence of b -- improvement for influenza b production.

the basis of the bad growth is not fully understood, but we have basic routine reverse genetics and molecular biology that shows that by swapping molecule's we can get increased fuel -- yield in h5n1. you see that one can actually design molecules such that the epitopes of the mural in the days of the original h5n1 are retained. once again, showing the feasibility that by using molecular genetics one can devise methods to improve a virus yields for bac vaccine production. we make so much vaccine from so

many different manufacturers, it is important to standardize the amount of ha in those vaccines. this process takes time. approximately one month during the normal production cycle to reach calibrate them and get them out to people. -- read calibrate them and get them out to people. -- recalibrate them and get them out to people. we set up a multi center collaboration, using not only the cdc but the colleagues at food safety. we have established a collaboration for the technique to determine the quantity in primary standards. we hope that this will be correlated with current methods, shaving time off of this relatively inflexible process of calibrating and redistributing

agents. it could shorten this part of the process from a month for several weeks to a few days. we are hopeful about this. the bottom part of the slide is to illustrate the current techniques used compared to the amount in the primary standard, using a mixture of total determinative gels. it takes several weeks to do this, where on the rise you can do a mass spectrum analysis by a matter of hours. a technique designed to improve the bottleneck in the process. another bottleneck in the current process for guarding the reagent production is the fact that you have to make a specific antigen for every strain in the vaccine. typically this works well, but antibiotics production takes time and requires that one be

able to grow the virus, pyrrophyte, put it into animals, and make it available. sometimes that does not work as well as one hopes. we have shown that as an alternative we can take for, and techniques in absence of the virus, using the techniques to make vectors and proteins, put them in the animals, the antibody will function as well as the traditional, the typical potency used to determine the amount of ha in the vaccine. here are a few examples from the most recent pandemic, indicated by lots 1 through 3. in each case and you can see a traditional serserum. we have an alternative to what

of the potential bottlenecks in the process. now i will turn my attention to ways in which we try to facilitate the development of new vaccines. as i said earlier, new vaccines are fundamentally different from current vaccines, requiring development of new tools. here we have a method we have developed to identify the particular protective epitopes the vaccine strategies. on the right if you look at the color coding, each little bar represents the epitopes and as you can see, down the slide each vaccine produces a certain number of antibody responses,

identifying a certain number of epitopes. responses include anti bodies and other parts of the ha molecule. this is showing that this is the new tool that allows us to understand the response to the vaccination and helps us in the decline, helping you to determine vaccination strategies by determining response of variation. finally, to repeat myself, then -- generation vaccines include other components. it is vital in advance of these becoming available that we have the tools to characterize the product and the response. shown here is something we have done over the last year or so, where we have improved the

ability to quantify responses to the virus. a possible component of new generation vaccines. on the left and you can see the current test tubes, each one has a sample. on the right you can see a 96 well format. on the right there is sensitivity shown specific for the type being detected. i will close here. that was my last one. i will emphasize again that influenza vaccine development and production is challenging. we and all of our colleagues are trying in many ways to speed up the current process and to develop ways to be prepared if new vaccines, mind.

-- new vaccines come onlin. -- online. >> thank you. i would like to open up to any questions. >> dr. goodman, your development for vaccine pandemic production , [unintelligible] >> it is a very complex issue. there are different laws and regulations in both areas. what you are referring to is the europeans that made a template made around the h5 vaccine that says that if you submit to us some initial data about a

vaccine that could function with any pandemic strain, we will meet you halfway to where you can plug in the vaccine that emerges and data will be limited. we actually do a similar thing. for example, when we do a strange hand, if we have previously evaluated the vaccine and vaccine technology, manufacturers can show us what was dropping out in to that. that is an accelerated process that can take days or weeks depending on the issues. i think that we have a parallel to that. our preference is to get as much information as possible before a pandemic, to understand the safe and effective nature of the vaccine.

if there is not enough data we can look at an emergency vaccine. but we do not want to confuse people about the vaccines that we have without being really clear. i think that it is partly a result of different systems and laws, a structure that we do something further. i believe that we were the first country to license vaccines in the world this year. >> any other questions? yes. >> it sounds like in the next couple of years these vaccines are going to become more complex. from the practical point of view in getting this out, will

this be setting the guidelines for what to use when and in whom? >> again, the answer to that is complicated. you are dealing with multiple products. the actual efficacy, safety scale of it alone is going to do a lot to determine the relative rank order of what will be used out there. certainly products will be submitted to the fda. i will leave it to jesse to amplify that. you know that the influenza that we give out seasonally, not many people fully appreciate that. what happens this year with the pandemic is very different from the regular years, where pharmaceutical companies with

licensed products produced it and it gets ordered to the tune of 90% of what is out there being a direct relationship between pharmaceutical companies and private distributors. so, it really is the competition of the market if you have a licensed product. i really do not see, unless jesse wants to contradict me, the federal government recommending a particular product amongst a group of products that are licensed by the fda. in the arena of a private enterprise, we will see a same sort of competition in the market did you see with any other product. >> i think that is correct. i think that the science will drive the public health recommendations and approval. it is very important to recognize that all of these

candidates may have optimal uses in different settings, populations, and different viruses. it could be very important for some populations and viruses, but not for all. we know that the live vaccine that was manufactured spectacularly well this year for young people, that vaccine has less evidence to support its effectiveness in the elderly. it is currently only recommended in children and young adults. we will have to see where the science comes out. it is true that once approved, the marketplace is the primary driver. our advisory committees and cdc advisory practices make it widely recognized as a public

health recommendations about what the best strategy is for using the available vaccine. eddie is an opportunity to have the science drive the best behavior. >> it translates into how they perform. data that tells you how they perform in different populations, in the past several years the advisory committee has discussed broadening the standards. now that there is increased capacity, even the potential that there could be an additional strain in it. the idea is that what we see is a whole new technology that is providing a new generation of vaccines that will perform differently. i think that what we hoped to see is those with the best performance having the best market. >> there is a question of mine. >> another question from mary mckenna.

could you please give additional details about which new technologies will require more changes in the immunity pipeline for bringing these changes to market? >> let me start. first, the way that the vaccine is working as by inducing a response against the standard portions of. we do not have new correlations in that area. i think that you will see again changes from what we see in clinical trials. when you start looking at molecule's where you do not understand the protective response, there are other concerns with matrix proteins

and nuclear proteins. ultimately we will depend on what we did previously on evidence from clinical studies, showing the effectiveness in protecting people against the flu. that will love hold up development, in a sense. but it will mean, and i think rightfully, that we have to see if it protects people. frequently that takes a large clinical study during influenza season. we are deprived of speeding up the process by a couple of years to one where we will have to follow a more standard process. " we are all doing to the extent that we can facilitate it, if we could develop clear correlates of protection for other

responses we might be able to do that sooner rather than later. fighting that science is what it is. -- i think that science is what it is. we cannot say something is effective until we know it is. >> any other questions? ok. that brings us to the end of the program. the video of today's session, along with a first -- description of the presentation will be posted online within the next few days. www.flu.gov. i would like to thank you all for attending, particularly our presenters for spending a couple of hours with us this morning. with that i will bring this session to close. thank you very much. [captioning performed by national captioning institute] [captions copyright national cable satellite corp. 2009]

now the chief actuary at c.m.s. is saying that >> and live picture from the floor of the u.s. senate, where they are addressing two items. earlier today they voted 60-34 to limit debate on the $1.40 trillion omnibus bill for the

spending on health care. while they are not officially working on health care this weekend, many senators have come to the fore to talk about the bill. most of the work continuing behind the scenes of the measure, formal debates are expected to resume on monday. you can see live senate debates on our companion network, c-span 2. >> now, a look at how technology impacts consumer policy. public policy groups discussed the benefits and risks associated with information sharing. the federal trade commission posted this one hour 10 minute discussion. >> this morning we heard from jim harper, david hoffman and

others, talking about what consumers really want from transparency. we are going to get the answers from this distinguished panel. this panel is going to address what we know about consumer expectations with respect to their use of information. we have heard that surveys have presented little value on this issue because they do not represent real consumer behavior. there is general agreement that consumers do not understand what happens behind the scenes. when using a loyalty card, they visit web sites for complete surveys. relying on actual consumer behavior to understand their attitudes towards and expectations about the collection and use of their information has limitations. the expert panel today is prepared to talk about these issues in light of their own research, as well as addressing the role being played from

disclosure in the vehicle of consent for commercial collection and use of information. first i would like to briefly introduce our panel. laurie kramer, on my left. next to her is alan davidson. jill kolineski from future privacy forums. adm searer. joe terro on the university of pennsylvania. allan weston from columbia university. >> may i intercede to say that we cannot forget about the consumers? [laughter] >> sorry. joe, kelsey, the consumers union. bias -- my apologies.

if you have a question for a panelist, right in on a card and it will be collected by the staff. those of you listening can e- mail us. we will be talking about a number of consumer surveys and studies during this panel. those are all available on the agenda. so, if you want to explore these issues in more detail, your welcome to find those materials there. i would like to throw out a general question. what do consumers know about data flow in the use of their personal information, online and offline? joe, we should start with you. i would like to have each of you talking about various research that you have done in your findings. >> at a high level, as you

said, there have been national surveys over the last 10 years. some of those studies have data about what americans know. it is not just their opinion. it is fair to say that generally speaking they know very of little about what goes on under the hood and online. the kinds of things that they do not know what surprised many people around here. particularly that americans think it is illegal to use discriminatory pricing. they believe that a company like expedient or orbits is required to give people the lowest amount of fair when they go online. they think it is illegal for supermarkets to change prices for different people during the same day. generally speaking, people

believe that the government enforces laws about privacy far more than a dozen. there is a sense that there are laws out there, people have this sense that there are laws protecting them far more than they actually do. >> have you found anything similar to that, joel? abou >> our research found a very similar results. for the most part they think that if the information being used is sold to target them, they think that they need to be given notice ahead of time. similarly with the government protecting the use of their private information. i think that they feel relatively comfortable that there is sufficient protection out there, when that is simply not the case.

the biggest concern that folks have comes from identity theft, the financial risk position. i do not think that they have a true understanding like we have on how the information is being used about them behind-the- scenes. >> mauri? >> we found pretty much the same thing. fighting that people have very little understanding of the policies and laws about privacy, and even how the information flows. a lot of people do not know what a cookie is, still. almost no one outside of this room knows about third-party cookies or flash cookies. when we do one-on-one interviews people are concerned about which part of the content on a wedge -- web page is advertising, let alone advertising that is tracking them. >> ellen, you have done a number

of studies over the years. can you talk about your high level findings and how consistent or different they are from what we have heard? >> my sense is that the surveys that i am familiar with over several decades are roomette -- remarkably in concert rather than conflict. all the surveys on the table here found that a majority of people, ranging from 50% to 80%, they say they are uncomfortable with behavioral marketing. they would want to have it at a minimum, notice and choice of security, ways of intervening that would give them some comfort if they were going to have their information track in that way. even though we are starting from a base of low knowledge by consumers as to how things really work, if you ask them about how they feel, they

believe pretty strongly that they are being abused and that this is not something they have bought into. the other thing in my survey is that it shows even though you can tell people that this behavior a marketing makes it possible the free things from the e-mail and internet benefits, we have gone to the point the way that the internet has developed that people take for granted. they are not prepared to make that into a real equation. in our survey we ask people, because of the ability to provide free services on the internet, advertising a test of possible, we tell them that what is going on and people are still not willing to trade privacy for the free things on the internet. >> alan, can you comment in terms of what to have found? >> thank you.

certainly it is clear that a lot more work needs to be done. i would say that a lot of work is being done right now. there is a lot of innovation in terms of trying to find ways to give consumers more information. consumers do not necessarily understand these issues and much can be done to give them more information. we can get into the examples, like the recent announcement from the auto, very similar to something we have launched to give users a chance to see more about what we know about them. that is an example of the kinds of things of the tools that will be out there for people to see what is being collected. that is just one of many examples of people in the industry trying to have interesting ways to inform consumers.

>> a jolt, you are one of those that has been doing this kind of work. can you talk about your findings with respect to what consumers no end expect? >> recently we did a set of focus groups and a 2600 user survey. when we tried to drill down specifically on advertising, moderately expert users were completely unfamiliar with the concept. a few experts consumers said he knew what it was. he wanted popcorn form watching a movie because there was a subliminal advertising. clearly lots of talking to people about privacy had not really moved the bar. what we started to see when we turned to the advertising industry, this is what seemed to

be such a debate. we asked if those skills could be used to actually talk to people. so, folks spent a ton of time with us generating language and symbols that we hoped to be effective at communicating to people -- and not anything about privacy, just how your information is being used for you. companies that advertise if they are doing good things. but what they are trying to do is sell you things without the word consumer to talk about people. they are trying to communicate something about what they have, using those skills. we are hoping that the output can be used by the industry. these are not about privacy and

how we are keeping things secret, but here is how we are trying to communicate with you and what resonates best. >> adam? something to add? >> for many years we have taken a hard look at the polls and surveys that have to do with child safety and free speech. we have expanded that and our message is quite simple. while these polls may offer interesting insights into how some people in the public think about privacy how advertising and so on, they are ultimately no substitute for real world experiences with real-world choices involving real money in real time. those experiments happen every day in the marketplace in ways

that we could not imagine if we have listened to the polls. people are living the lives like open books on social networking sites, giving away information, if we have asked a few years ago with these people would have done these things that they would have said absolutely not. privacy is a subjective condition and there is a lot of trial and error out there. people themselves personally experiment with how much they would like to give away about themselves in exchange for something else. there is no free lunch. sometimes it means we have to give something to get something. sometimes that is information. there is a rational ignorance at times in these markets. we might say one thing about what we think about something, we might do a different thing if we have our own time and money in on it. >> laurie, what about this

disconnect between the online behavior consumers exhibit on a daily basis? and what we hear in the polls? is this truly a disconnect in what consumers are doing? does it really represent their view towards privacy? or is there something more going on? >> there is a truth to the fact that there is only so far you can go with a survey. you can still learn a lot from surveys and we do understand that about attitudes. if we look at behavior we have observed all sorts of things about the real world, but it has not been set up as a controlled experiment. we have had situations where people do not understand the consequences of their actions. so, people are behaving in the real world based on information.

that by itself is not giving us the data that we want. but at carnegie-mellon we have tried to facilitate experiments where we could measure people's behavior in a controlled manner. this is hard to do in the way that you have valid data, but we have been able to show that if you annotate search results with website privacy policies, people will pay more to shop for the web sites with better privacy policies. these kinds of experiments, and i would love to have some of the company's working with us so that we can have a large sample of users. larger than what we can get at the university. >> any response? >> we would love to work with you on something like that. [laughter]

just to give an experience of our own, recently relaunched a product this spring called interspace advertising. some of you probably heard about it. we had a hand out in the back that was a screen shot. the idea was to be responsive to the concern that people do not understand what happens when we do interest based advertising targeting. the first was that when you see an advertisement that we have helped to place there is a link to get more information. second, the privacy center that shows you the user using all of the target signals that we used for targeting that advertisement. then there is the ability for the user to change the signals. things like we think you are a sports enthusiast or we think that you like interior design

based on your web site behavior. we let people opt out and change it. you might say that you are not a sports and tuesday as but i am interested in automobiles. for cooking. we have had this out for about -- well, since the spring. what we have seen is the site getting hit by tens of thousands of people every week. tens of thousands of unique visitors each week. the behavior has been interesting because we had the assumption that people interested in privacy would be opting out. but a lot of the people that come to the site actually change their preferences rather than completely opt out. so, people are arriving, but not

opting out. what they're doing is playing with it. so that they can see what happens if they change the preferences. actually, 10 times as many people do nothing. there are a lot of things that you can read into this. but to simply say that people are not informed and if you inform them we will get rid of these things, this is a different view. will we ever heard is that your mileage might vary in terms of what your consumers want. and how they feel about privacy. what has been interesting to us is that if you and our people, they might start to exercise their choices. many consumers do understand that there is a bit of a bargain here. in that part of the reason that all of these amazing free services exist is partly because of the advertising that supports

them. there's a lot of work to do to unpacked this, but there will be more experiments like this in the marketplace. it will be interesting to unpack how people use them. >> joe, do you have any additional information? >> i wanted to suggest that while i understand what google has done with the categories, it is important to realize that from the standpoint of a consumer, those are marketing categories. you go to that website and first of all it appears incredibly benign. that makes people that worry about privacy look foolish. it says you like bicycles. or it says that you like water skiing. yes, you can target for it or not. what is not shown in this kind of thing, possibly because who will does not do this sort of thing. the various kinds of psycho

graphic, demographic activities that go on behind the screen to yield these categories. or the tiny things that many companies do to supposedly anonymously grab people's plan -- financial information, using it to create profiles. it looks like this is something that talks about whether you like bicycles or cars. but i think that that is not a correct assumption or set of projections about what is happening in our online and offline world. >> jules? >> my responses this. i think that what we are seeing, hopefully, what the economists debate about these things being accepted even if they're not free, there is a potential user here. when users interact with the

kind of tent -- tailoring that they like, whether it means they understand what happens at amazon, clearly it works. can any of these models, despite that the fact of their operating as third parties, can any of them make data used from the feature? can they succeed at being an honest depiction of what is going on without it becoming incredibly complicated? i would hope that they do not become a dashboard. as complicated as it can get. my argument is, can we agree this is what has prevented these from happening until now. it would have been too hard to show their profiles in the early days accurately. figuring out how you create a feature that succeeds in the market so that people enjoy it

and play with it. today both the of who and the at&t yellow pages went live with the version of this little symbol that leads to these advertising preferences. you are starting to see people doing it in different ways. we will see if users like it, turn it off, and hopefully the kind of feedback -- i do not like this category, why are you doing it? this would be the first step of development in the market. we need to future rise, not hope that interested people care enough to find their own data. >> i would like to go back to looking at real world choices and that idea. i think that we see a lot of consumers making real world choices when it comes to

answering the cost benefit question of free content verses giving up information. havmany consumers try to protect their enemy -- anonymity by the leading cookies, giving false information, using false e- mails. consumers are growing to great lengths to try to protect anonymity. and then we see the market response in the financial incentives, respond in the flesh cookies and things like that. so, a lot of these things, there were the real world experiences of data breach security problems. a lot of this leads down to a place where we need regulatory framework that provides more transparency to talk about what

kind of data is being collected, what is acceptable and not acceptable in terms of what is being collected and how it is being used in. -- in the end. >> those are simply the categories that we are using. for example, there are categories in the advertising that we do not have. we do not have the same information to target the financial information. it speaks to the fact for the need for greater transparency. i do not wanted to sound like this is an isolated and coincidental case. google has a product called a dashboard that lets you see more about all of the information that we keep about the account

holder. facebook has been a cop -- pioneer. we expect that there will be a lot of experimentation in the market. there are some very sophisticated players out there that have a great desire to meet this demand to give people more control. we think that transparency and consumer choice is going to be a foundation of fair information practices. >> in order to match the sources you are providing with what consumers have said, do we have an expectation except to say that the companies that are being dealt with directly, do they -- is there any information about their expectations in terms of further use of that information from other

companies that are behind the scenes? do consumers even know about this? what would we understand their behavior to be? assuming that we did, i am trying to differentiate what consumers expect with respect to information on different levels and different types of information. if you are just going to purchase a toy online, that is very different. jules? joe? do you want to start? >> i will try to be brief. these studies show a tremendous concern, the radical concern. no one has played with a dashboard as suggested and said that this is working or not working. so, to tell someone -- guess what, someone tried to do this thing that you did all day, of course you have a negative answer.

the question is, can we bring that into public view so that users can actually get their hands on it, we get, and we get a good sense about what they like and not like? one of the things that i do not like about the interest manager in yahoo is that it shows you something that everyone knows. it has a general idea of where you are. not only are these things that we think about you, there are other things that we care about. of course, we all know that you can geo target based on ip, but people still wonder why there are cuties in potomac that want to meet me. how did they know that? [laughter] we think that you are generally here and i think it is a great

de mystification. we do not really know what things will be like when they start to click and play. facebook, we always talk about begin examples. the most interesting example is not beacon, but it might be why it happens -- my god, instead of seeing around page in having to visit your friends, all of this stuff about what happened is all on your page. there was an outcry, we were stalking our friends. if you had asked anybody that would have thought it was terrible. now it is like why we go, so that we can learn what people are doing. i think that you need a little bit of room for letting people delight users with new ways of

engaging each other and making sure that we are not surprising them once we understand what they like. >> we found that, for example, it is not just the online world. i do not think that there is a difference between online and offline anymore. most americans do not realize that supermarkets have the right to sell their data. they probably have no idea that supermarkets collect an enormous amount of that information. another important issue that you brought up, how do people know to cross the companies even if they trust the companies? you may have seen a piece in the times about a company that other corporations contract with ford discounts for employees. why not? it sounds like a great idea.

apparently they have been collecting enormous amounts of data about the people that get discounts. using that information to deliver advertising and whatever else they are going to do. that is the kind of thing that would be hard to know if they had any clue this was going on. and whether there was a policy presented to the people. it is a difficult scenario to imagine. how do we know that companies are being straightforward? >> palin davidson, i would like to bring some things to you. you said that you do not use sensitive information. can you explain what you mean by that? before do get their, can you give us any sense in terms of the percentage of the total

number of visitors to the will? how many of them have gone on to the advertisement purposes website? >> i do not have an exact number, but i would say that it is small. tens of thousands of each week out of the many more users. there are many points that one could take from that data. it also might be that this is something that users probably do not necessarily interact with on a regular basis. if we do this right for a lot of users it is the kind of thing where they will set their preferences to where they feel comfortable and not have to think about it again. i do not think that we necessarily expect a lot of the current traffic. others will draw that conclusion.

with sensitive information this is an important area with guidance from the commission that has been helpful for the future. for example, this is all within the narrow context of advertising in different ways. we do not use signals about certain categories of sensitive information that we believe are not appropriate for use. health information. information about sexual preferences. information regarding children. if there are others in the room, the finding those is really important. we had an earlier panel about why people might want to do that and we have made a choice not to. it is appropriate for this kind

of advertising from our perspective. people feel that this is an area where clear guidance from policymakers can create a bite -- baseline for users. >> if i could push that to understand better, when you say health information, if someone search for alzheimer's -- >> you would see, and anyone can look, you can search for it of bing and it will come up, actually. [laughter] the fact is, this is the easiest way to know this, if you simply look at the categories you will not see something that says alzheimer's patient. you will love see anything close to that.