 Good morning and welcome to the CSIS conference today on the Strategic Power of Vaccines. I'm Steve Morrison, Senior Vice President and Director of the CSIS Global Health Policy Center. It's very heartening to see so many friends here this morning and I want to offer a welcome to the 150 or so people who are joining us online. My boss, Dr. John Hamry, sends his regrets and unforeseen circumstances pull him away. So I'll be doing all of the opening remarks here. Special thanks are due to several people. Among my CSIS colleagues, I want to single out Seth Gannon who has worked assiduously and indefatigably for the last several months in pulling all of this together and done a masterful job. Matt Fisher, Julia Nagel, Margot Reeves, Carolyn Schroet, Hanadanji have all contributed very much to today's events. Many other friends have helped us. I want to single out particularly Amy Batson from USAID, Patricia Conrad from NIAID, Margaret Lidstone from Yavi, Alex Palacios from the Gavi Alliance, Deb Derrick from the Bill Melinda Gates Foundation, and Chris Elias from PATH Decade of Vaccines, and many others have helped us. The day's program today features the very best, the very best in terms of experts and leaders and people of astonishing personal commitment and drawn from a variety of places, from the U.S. government, from international alliances, the business sector, the foundation, and university worlds. We're greatly indebted to each of our speakers for taking their valuable time to share their thoughts with us today, and we're very reliant on all of you for your expertise, your generosity, and your continued friendship. This is the second high-level forum on U.S. leadership and global health that we're holding this year. The first in March was really looking at the value of global health investments. Today, we've chosen, and I'll explain why in a moment, we've chosen to examine immunization as an essential component of U.S. leadership, and as a critical tool to advance U.S. national security and economic interests, and to advance the broader human security of the world's populations. We chose this date for a couple of reasons, and we chose the subject. First of all, this has been a very good year for immunizations and vaccines. We've seen the surprising and very heartening success of the Gavi Pledging Conference in June of this past year. We've seen the continued march forward of the decade of vaccines efforts. There's increased attention. There's increased momentum and hope, and related to that, we've had with respect to HIV-AIDS, Secretary of State Clinton's speech followed by President Obama's speech December 1 on HIV-AIDS, on an AIDS-free generation, on beginning the end of the HIV epidemic. This has had a very profound, a very profound positive impact in renewing people's enthusiasm and focus. Vaccines we all know need to have a better face, a better brand, a better understanding among policymakers and among the public. Our basic premise today, as we move forward, is the same as in March, which is that strong continuing U.S. leadership in close enduring partnerships with others remains essential to global progress. Another core premise is that the vaccines are fundamental to human security, and we mean that in respect to conflicted areas, to areas that are more stable, and in times of austerity, they remain across those settings indispensable cost-effective best buys. We believe that we're in an era that's exciting, an era of continued innovation and discovery, and that as part of that process, the private sector remains fundamental to generating vaccines that do more, cost less, are more easily delivered, and address diseases that have never been before able to prevent. We'll hear much today about the complex and delicate scientific business and policy partnerships that are essential to stir innovation in our global economy. We'll hear more about the competing priorities of balancing profit and deep long-term strategic investment with the need for addressing inequities and producing high volume and low cost. This is not easy work. It's not for the faint-hearted. Public trust and confidence are often very fragile. Finances are not always secure. Supply change and skilled personnel can be scarce. Trying to create a truly coordinated global strategic plan we've seen can be daunting. And as I said earlier, the broad public understanding, the branding, the face of vaccines still is something that needs considerable work. This brings me really to the defining message, I believe, for this day's conference, which is we're in an era of great forward movement in which vaccines figure ever more significantly in U.S. leadership and our national interests and in the discussion of how to advance global human security. There's much to be proud of. Much excitement as we look to the future and expectations are high. As we move through our program today, we'll be covering these issues through individual speeches by Dr. Anthony Fauci, whom I'll introduce in a moment, three distinguished high-level panels, and a closing speech by USAID Administrator Rod Shaw. We've also issued two papers today that I hope you'll enjoy reading. We have hard copies. They're available online. Dr. Phil Nyberg, a very close friend and ally of ours, and Nancy McLaren, authored Role of Vaccines and Immunization Programs in Global Disease Control, and Dr. Stephen Kachia, CDC, authored the Future of Global Immunization, Will the Promise of Vaccines be Fulfilled? We're going to open today with a very brief four-minute video. It's a trailer from a broader project on Zambia. This is a fresh video that was put together by a CSIS team last month that visited Zambia. The reason we're opening with this is to remind ourselves of the ground-level human reality of immunizations. We wanted to begin the day with voices of Zambian mothers, doctors, and leaders, and their partners in this trailer, and to hear their compelling testimony as to the power and impact of vaccines, particularly for maternal and child health, and speak to the importance of achieving broader development goals and addressing the enduring challenges. Janet Fleischman, expertly guided the filming of this, joined by Emma Curran, Julie and Nagel, and Seth Gann, and we're very grateful to them. We're also very indebted in putting this together to the cooperation of the Zambian Minister of Health, Joseph Cassonde, to U.S. Ambassador Joseph Storella, and his Deputy Stephen Schwartz, and Public Affairs Office Priscilla Hernandez. We've also received extensive support for which we're very grateful from the Zambian Embassy here in Washington, and we're joined here today, and I just want to offer a special welcome to the Zambian Deputy Chief of Mission, Alfred Chioza, and Ben Kwankwa, the press attaché. So thank you very much. This product will be issued next month in a final version as a 10 to 12-minute video. If we could begin the video, please. It is very important that we see development as a human development. It's not that we should have tall buildings. It's not that we should have only nice roads on which we can travel. It is above all that we develop the human beings. And if we're going to develop human beings, it is logical that we see development as starting with what we do with the children as they're born. It is through vaccines that we have been able to protect the health of the child. What you see in immunization is very simply prevention. When children are immunized, they don't get sick. When they don't get sick, they don't spread the disease to others. These investments in immunization, which sometimes can cost as little as under $20 a year, can protect the child and a population for years. The immunizing children, protecting them from preventable diseases, I think that's incredibly important. And there's a lot of children and women out there that aren't getting the benefits of these services. We've got a huge geographical area with very few people in it. The topography is difficult to navigate. The road infrastructure is lacking. And often people really don't have very regular or frequent contact with the health facilities. People have to walk long distances to go to the health facility, and it's not easy. So when their mother is bringing those children for health services, she might not be able to carry two, three children because she has to walk long distances. Zambia is a huge, huge, expansive country such that in certain places you may not actually have, say, electricity. So the sort of coat-chain equipment you use has to be tailored to that local context. When we are going to conduct these outreach activities, we make sure that we carry enough ice packs so that we maintain the coat-chain. Most of the health centers are run by just maybe one nurse only. But for a center to run, you need about three trained staff. You may actually appreciate that it's quite a challenge to ensure that vaccines are delivered in the remotest parts of Zambia to these women and children. In our program on vaccination, it has become very apparent that it is the one area we would never have succeeded without partner support. So here we have a situation where we accept responsibility for the core support of the programs, but also appreciate very much the support that we are getting from our partners. Immunizations are important for the development of Zambia. I will give an example of myself. I have a big scar here, which was given to me when I was in primary school for smallpox. Now it's history. My children, my grandchildren, will not know of smallpox because it has been eradicated. It's not going to happen overnight, but by having a strong partnership with a country like Zambia, a country that's on a strong democratic path, we really can reach that point. Eventually we're beyond assistance, and that's what we're looking forward to. As the motto says, children are our responsibility. All of us, we are very much responsible for the children. So as you may be aware, these children are the future leaders. These are the future presidents, the future pastors. So we make sure that these children, they grow very healthy and provide positively to the running of Zambia as a country. Thank you, and congratulations to Janet, Emma, Julia, and Seth. Last month, in early November, I was in Fukushima City in Tokyo, and there was a lot of discussion around how to resolve very controversial outstanding issues around safety and science related to low-dose long-term radiation, and how to rebuild public trust and confidence. And there was a frequent lament in Japan that I heard that there was no revered public health and science personality who could transcend the divisions there and speak authoritatively and command broad public trust. And the lament often concluded with a comment, you wouldn't understand our problem. You have Tony Fauci. So I just wanted to mention that, Tony, because it actually did happen, and as a way of introduction, we have asked Tony to come and kick off this conference with a keynote address offering his reflections on the state of vaccinology, looking backward and forward. And I don't think there's anyone better and more authoritative and respected in this field to fill this role. He serves as director of the National Institute for Allergies and Infectious Diseases at the National Institutes of Health. He's been in that role since 1984. He has been a key advisor to presidents and secretary, cabinet secretaries on a full range of issues around preparedness, clinical research. He's made many seminal research contributions across a very diverse portfolio. He's widely published. He's the winner of the Presidential Medal of Freedom, 36 honorary degrees published over 1,100 articles. This is one single man. I'm not sure quite how that happens, Tony, but we're thrilled to have you here today. If you would please come up and please join me in welcoming Tony Fauci. Thank you very much, Steve, for that kind introduction. It's really a great pleasure to be here with you this morning to discuss the subject which Steve has so nicely introduced, namely vaccinology. I chose as the title of my talk, Considerations for the 21st Century. But before I do that, I'd like to just put it into some perspective about where we've been and where we are now and what we have to look forward to in the future. And for the sake of some order and clarity, I decided to break up my relatively brief presentation into four major components addressing vaccinology and global health. The economic impact of vaccines, the scientific issues that we face today, and the future of the scientific approach to vaccinology. And then finally, some future considerations for the field of vaccinology in general. So let's start off with the issue of global health. I don't think I need to convince anyone in this room about the importance of infectious diseases worldwide as a global health issue. As you know, about 25% of all the deaths in the world are due to infectious diseases. It is the second leading cause of death worldwide, the leading cause of death in people from birth until early adulthood, and also it is the leading cause of dalleys. So to say that we don't have a global problem is to not understand the issue. Importantly, if you look at infectious diseases and their impact, it is really quite discordant in that if you look at the number of deaths in high-income countries due to infectious diseases, about 6% in contrast in a region such as in sub-Saharan Africa, greater than 60% of the deaths are due to infectious diseases, the important point that we're all familiar with is that many, many of these, if not all of them theoretically, are actually preventable. Preventable because we already have vaccines for them or preventable because we can have vaccines for them. If one looks at this somewhat historical slide here, which really hasn't changed over many years except for the addition of some of the diseases such as H influenza B, which I'll get into in a moment, the impact of vaccines in the United States, which is a reflection of the developed world, is truly stunning in the history of the translation of biomedical research to practical countermeasures. The numbers speak for themselves. If you look at the right-hand side of the slide, the percent decrease in these diseases globally is something truly of historic importance. If you take those numbers and look at them a different way, you can come up with the following important data that of each U.S. birth cohort within the current childhood immunization schedule. It can prevent vaccines about 42,000 deaths and about 20 million cases of disease. And the newer vaccine impact, such as pneumococcal vaccines and rotavirus, are really comparable to that with over 200,000 serious infections and 13,000 deaths prevented over an eight-year period from 2000 to 2008, and the most recent routine rotavirus vaccination preventing up to 60,000 hospitalizations per year in the United States with an even greater impact globally. Speaking of the global impact of vaccines, immunization prevents about two and a half million child deaths in the developing world and about 20 million lives saved over the past 20 years, including from the following, measles, polio, neonatal tetanus, and reduction about 35% since the institution of the pneumococcal vaccines. So from a global standpoint, not only is the impact extraordinary, but the potential is even greater. I just want to point out three recently developed vaccines and their lifesaving potential in children. I know you're familiar with these, the pneumococcal conjugate, the homophilus influenza B, and rotavirus. Right now, the impact of these three infections, if you look 10 years from now, if I were giving this talk, I think these would be then relegated to the diseases that had a 99 to 100% decrease. Let me give you an example of that, and this has to do with the implementation of programs. Take the middle one on this slide, homophilus influenza B. In the United States, as again I'm sure all of you know, that H influenza B is the leading cause of microbial related mental retardation and deafness in children. We are at the point now that we can really look at the potential elimination of this disease. If you look on the left-hand side of the slide with the United States, that the incidence of hip cases has gone down dramatically. If you look at the right-hand slide in Uruguay, we're seeing the same thing. There's no reason to believe that in the developing world, we're not going to see the same results that we're seeing here in the United States, which leads to the potential for another potentially eradicable disease. So let's move on to the second item that I'm discussing, the economic impact. You can look at economic impact from two standpoints. The economic impact of not having to take care of sick people, and the economic impact of people who might have been sick, who are now well, who are going to have a positive impact on the economy. So if you look in the United States, the vaccination, again, of each birth cohort is going to save over $14 billion in direct costs, as well as close to $70 billion in total societal costs. If you look at the global impact, take an example, the classic historic example that was mentioned on the slide, on the video, eradicating smallpox cost the United States about $100 million over a 10-year period, leading up to the 1977 eradication. And that investment alone has saved us already over $1 billion per year in treatment and prevention costs. And globally, the savings of vaccines were estimated in the tens of billions of U.S. dollars in direct savings. The other side of the coin that I alluded to a moment ago is that there are other economic benefits as to do, for example, with labor productivity. So if you immunize 90% of the children in the 72 most poor countries, you could prevent 6.5 million deaths, 420 million cases of illness, and save billions and billions of dollars, not only in treatment costs, but as I mentioned in productivity losses. So again, the economic impact speaks for itself. Now scientific issues, this is really critical because we are now in the 21st century entering an era where we can take an already successful program and make it even more successful. A recent, this past summer, publication in the journal OMIX, we're talking about the top five what they call game changers in vaccinology, which are directed towards a rational vaccine development as opposed to more of an empiric approach. And we're using now technologies that are just starting to be applied to the field of vaccinology, such as immunogenomics, next generation high throughput sequencing. We can do things now with the sequencing of microbes that were unimaginable just a few years ago, other cutting edge omic technologies, bioinformatics, as well as the systems biology approach to immune profiling and vaccine responses. And I just want to take a moment to just flesh that out a bit. When you talk about systems biology, you're talking about multiple facets of the host, which you can learn from to help direct the vaccine development. I mentioned just a moment ago the issue of sequencing. It is really astounding that things that took months to a year to do, we can now actually do in a day, for I can't even figure out the percentage of the cost. The first microbe, the first bacteria that was sequenced by Craig Venter years ago, hemophilus influenza B, took about a year and a half to do for about $25 million. We can do an E. coli now in about seven hours for about 25 cents. So it just boggles the imagination of what you can do now with our sequencing capability. With that as a background, the gene expression profiling the multiplex analysis we have in our systems biology approach with cytokines and chemokines, multi-parameter flow cytometry and computational modeling, these are not things that are really confined to a few people. We have people in many laboratories throughout the country who do this routinely. Another issue to bring up again, I know that you're familiar with, but it is really extraordinary if you look at what we can do now in the 21st century compared to what we did. When we first had recombinant DNA technology, you would take a protein that you knew was an immunogen, you would clone the gene for that protein, and in an expression vector, you could make that protein. So that's using genome-based vaccinology. A very important paper a few years ago by Rino Rapuoli introduced the concept of reverse vaccinology because you have the capability of essentially sequencing and expressing every gene in a microbe, getting the proteins that are coded for, and then figuring out what the best immunogens are, and that's what he did with the meningococcal vaccine that he so successfully worked with. I want to use HIV vaccinology, which is frustrating because we don't have a vaccine. I'll get to that in a moment for HIV. To just mention the prototype of the challenges that we now face with vaccines or diseases that are not going to be low-hanging fruit, one of the beauties of vaccinology is that you learn from nature. In classic vaccinology, the response to natural infection directs you with its own natural proof of concept as to where you want to go with the vaccine. So if you take smallpox, if you take measles, if you take polio, we know as a proof of concept that the body, even though you get sick and can die from that, really will ultimately make an immune response that will clear the infection and will protect you usually lifelong from subsequent challenge. So nature has already done a lot of the biomedical research work for us. Not the case with HIV vaccinology because we don't have a proof of concept. In fact, the body doesn't handle, from an immunological standpoint, HIV very well at all. So what we need to do is a combination of empiric and design of a vaccine to do better than nature. Recently, there was a trial a couple of years ago referred to as RV-144, which actually was the first signal of efficacy, modest though it was 31%, not ready for wide distribution at all, but a proof of concept. So that's the typical example of doing something that isn't all empiric, but has a large empiric component and then go back and try and figure out what the correlate of immunity is and we have some very nice clues of that from Nelson Michael and Jerome Kim and Bart Haynes and others who are really studying this intensively that there may be now some clues how you can identify one of the correlates of immunity, at least of that vaccine. However, we need to even do better than that, not that that's not going to be an important part of it, but we know now that there are some correlates there. What about prospectively looking at inducing immunity that we would predict would be protective, namely improving on natural immunity? Peggy Johnson, my colleague at the NIH and I, wrote a commentary about that in the New England Journal just a couple of months ago on that and what we were really referring to was structure-based vaccine design. And for those who are not used to looking at the slot, I apologize if it looks a little confusing. What it really is is a molecular designation of the envelope of HIV and those bars that are going like CD4 binding site and quaternary epitopes, et cetera, are the sites in which we know the body has made neutralizing antibodies against. They do it poorly. They don't do it frequently enough, and they do it too late, but the body can make antibodies that can neutralize against those epitopes. So what scientists are doing now is by doing a variety of structure-based, high sequencing, high throughput cloning, are able now to identify a large number of neutralizing antibodies, specifically identify the confirmation of the epitope to which that antibody binds. And the big challenge now, and you're going to be reading about this, I'm sure, over the next few years, is to take those neutralizing epitopes and make them immunogens, namely something that will induce a response that for reasons we still don't appreciate, the natural response to the virus doesn't do. Bottom line is we have to do better than nature. Let me move on quickly in the scientific arena to the importance of employing existing and exploring novel adjuvants. We have not, certainly not in this country, used adjuvants to the extent that most of us feel needs to be used. Now, from a very simple standpoint, we know that what adjuvants do is they reduce the amount of antigen needed. That's good from a production standpoint. It promotes earlier, stronger, and more durable immune response. That's good from a host-defense standpoint. And importantly, it may increase cross-protective immune responses, which we've actually seen glimmers of in the influenza vaccines that have been given together with adjuvants. Right years ago, we used to think adjuvant is a boost in a very simplistic way, not really sure how that happened. We now know in the science of the 21st century that, in fact, what adjuvants do is they call upon molecules that literally, evolutionarily, forever have been used as part of the innate immune system, trigger that, which is a bridge to the adaptive immune system. So adjuvants have a very specific molecular mechanism of why they work. And there's an extraordinary amount of information that is being accumulated right now by the study of the innate immune system and this relationship to adjuvants. So let's now go to future considerations. And I will close on some considerations in this category. These are four important diseases in which we lack a vaccine. I already mentioned HIV-AIDS. In some respects, the same holds true for tuberculosis. As ancient a disease as it is, we still are somewhat in the dark about the immunopathogenesis of tuberculosis. We don't have a vaccine that's effective against pulmonary tuberculosis. Malaria, there have been some very exciting findings over the last months to a year and we look forward to that. And then there's the whole arena of neglected tropical diseases. So we have important challenges for us in the 21st century. To give you one example of this issue that I alluded to just a few minutes ago about inducing something that isn't natural to the immune response. I refer to it as unnatural immunity. Sounds a little ominous, but really what it is is to get the immune response to do better than what it does against the natural infection. A typical example of why we need to do that, and I believe we will be doing it, and I'll give you some examples of why we're there, is the whole issue with seasonal influenza and the need to every year update the influenza vaccine because of mild drifts in the antigenicity, particularly of the hemagglutinin molecule. And then every once in a while, we get a crisis like we had with the H5 and still do with the H5N1, and that we had with the 2009 H1N1, where we have the emergence of an influenza virus that is different enough that we don't really have a lot of background immunity and we don't really have a vaccine readily available. What this screams out for is what we are doing now. When I say we, I mean the scientific community, the Department of Health and Human Services, particularly the CDC and the NIH and others in our international colleagues, are really diminishing if not getting rid of the barriers between seasonal influenza and pandemic influenza. How do you do that? You do that by getting a vaccine that actually has the induction of a response that's good against any influenza. So again, it's a little bit complicated slide, but I just can't help myself showing it to you because it's such exciting science. Is that the immune response against a typical influenza virus and influenza vaccine is against the hemagglutinin? The good news is that it's immunogenic and it makes a protective response. The bad news is that most antibodies bind to epitopes that are highly variable. However, in the stem of this head stem molecule, as you see in the lower part of the slide, are epitopes that really don't change very much. They don't change in a drifted strain and they don't really change if at all in a shifted strain, namely a strain that would be a pandemic. So antibodies that neutralize these areas there and bind to a conserved region are antibodies that would practically, in the real sense, be able to protect against any particular influenza. And in that regard, my colleague and I, Gary Nable, did a commentary really summarizing the work of many people, including Gary himself, that we can actually again induce unnatural immunity. And why do I call it unnatural? Because when you get exposed to influenza, the confirmation and typical physical association of molecules makes it very difficult for the immune system to see that part of the molecule that is conserved. And now by using techniques like DNA prime and standard boost, you can actually induce the body to make a response that it doesn't see in natural infection. Hence, we use the terminology unnatural immunity. Now, also as we know, Rina Roperoli and his colleagues, and he gives a great talk on this, talks about a new way of looking at vaccines. What he calls it is vaccines for the 21st century. And saying that vaccines now can address the new needs of the 21st century society which is not only the classic protect children from childhood diseases and occasionally adults, for example, with the pneumococcal vaccine. But take a look at society, look at the increased life expectancy, emerging infections, the diseases of poverty and have a whole new paradigm about how you look at vaccines. And again, these are busy slides and I certainly am not going to go through each and every microbe on the slide. But what we talk about is a vaccine for every age, pre-birth, vaccines that we classically have done for infants and children. Vaccines for adolescents, such as things like the human papillomavirus and the impact that it will have on cervical carcinoma. Adults, elderly, travelers, patients with chronic diseases. Obviously people with HIV who are susceptible to other infections. And then the whole host of emerging infectious diseases. And then finally, vaccines, what we would say, should be given in the setting of poverty, particularly for many of the neglected tropical diseases which we know so profoundly affects the bottom billion of people in this country. There's also vaccines for cancer. I'm an infectious disease person and I've thought about vaccines always in the context of microbes. But over the past couple of decades, we now have a very strong push with appropriate scientific backing to look for vaccines for cancer. Some of the examples of these are on this slide. The ones with the asterixes are ones in which we already have a vaccine. Most recently, there's been a considerable amount of justifiable excitement over the human papillomavirus and the impact that it would have on cervical cancer, particularly in the developing world. The history of hepatitis B and its important impact ultimately not only on the disease, but on the development of hepatocellular carcinoma. And then most recently, we at the NIH, in a nice collaboration between the Infectious Disease Institute and the National Cancer Institute, is that Harold Varmus and Gary Nable and I and Jeff Cohen and some of our colleagues held a conference about the importance of getting a vaccine against Epstein-Barr virus, not only for the protection against infectious mononucleosis, but also because of the multiple neoplasms that are associated with Epstein-Barr virus. So what we now have essentially in closing all of those four issues, but we can achieve this and the global immunization goals. Obviously you need the science for that, but there are a number of vaccine initiatives and these are just a few of them Steve alluded to. Some of them before the decade of the vaccines collaboration, the Millennium Development Goals, the US Institute of Medicine Consensus Study in which they identified and prioritized new prevention vaccines for developing. The decade of the vaccines have had the privilege of being on the Leadership Council, which involves WHO, which involves UNICEF, which involves another agave and a number of other important organizations. So I'm very optimistic that this is going to provide the incentive to move forward. The Pacific Health Summit that I went to last year was really a very, I think, exciting experience. I show this because I want to close with this slide. We have been working with the Bill and Melinda Gates Foundation and with other organizations for a considerable period of time now. But the reason I liked what was said at that conference and I'll just give a quote from one of the things that I took out of it and read it to you in closing, that the successes of vaccine really do as I've tried to allude to in the few minutes that I've had with you this morning. Stand alone in the enormity of the impact they have on global health. Anytime you talk about a scientifically based intervention on global health, vaccines is always in the top two or three. In fact, it's always number one. I don't want to be too provincial about it, but it is essentially number one. However, we really can't rest on our laurels. Many important challenges remain. We have at our disposal the scientific tool kit, some of which I've mentioned, just a bit ago to meet the challenges and to elevate the field of vaccinology to unprecedented heights. From a scientific standpoint, it's interesting. We've been so successful that in some respects, not all, but in some respects, we've let the science of vaccinology lag because we did so well with it. What we really need to do now is bring the science of vaccinology squarely into the 21st century, and then I think the results that we have will far outstrip the historical results that we've seen over the last many decades. Thank you. I don't see Steve, but I think I'm supposed to take, there he is, all right. Yes, Alan Moore with the Stimson Center in George Washington University. Thank you for that. I didn't quite get all of the science, but I'm hopefully not the only one here who didn't. Next summer, Washington will be full of thousands of people here for the International AIDS Conference. You talked about AIDS, and I guess I'm wondering if you can say a little bit more about the outlook as you see it on the hope for a vaccine for both the international community and the domestic community. The President made some very positive comments for World AIDS Day. Can you expand a little bit on the message of hope or realism for the international AIDS community? Yes, well, I will be delighted to do that. Interestingly enough, we're at a vaccine conference now, and the vaccine is not going to play heavily into the theme and spirit of what we're going to be talking about in July. And let me explain what I mean. It isn't that vaccines is not important. It remains the holy grail of scientific accomplishments for HIV AIDS. But right now, with Secretary Clinton said at her visit to the NIH on November the 8th, when she spoke of an AIDS-free generation. And what the President himself said on World AIDS Day here in Washington about increasing the benchmark and the goal for a number of people on therapy is that we already have within our grasp right now, if we implemented properly the wherewithal with treatment and prevention together. There was a tension between treatment and prevention. What should you do for prevention? What should you do for treatment? Now we know that if you take treatment as a prevention tool, because you can actually treat people and know very clearly from a very, very good study that you could remarkably by over 95% decrease the likelihood of transmitting infection from an infected person to their uninfected partner by getting the viral load low. And you scale up things like circumcision, mother to child transmission prevention, proper use of condoms, that if you mathematically model it, you can actually see the decrease in the trajectory of the pandemic to the point of going down to elimination. That's the great news. So you say to yourself, what has that got to do with vaccine? What it has to do with vaccine is that you can change the trajectory. But given human behavior of prevention and adhering to treatment, that as the malariaeologists say, you can control malaria. You can even eliminate malaria. And hopefully we can eradicate malaria, as Bill and Melinda Gates have said. I think what we're talking about with a vaccine for HIV, if you really want to eliminate and hopefully eradicate HIV, you're going to need a vaccine. That's not going to come for several years, because we still are in the discovery phase as opposed to the implementation phase. So what I'm really trying to say is that the July meeting is, I hopefully will articulate well, that we can implement things that we've already scientifically proven and have a major impact. But we've got to do the science to get a vaccine to really put an end to the pandemic. So that's the way I look at it. One is implementation of what we already have, and the other is the scientific discovery to give us a vaccine. Yes. Matt Lawler from BART at HHS. Thanks for that great overview. I was curious about one thing in the Zambia video that you didn't touch on in your talk, which is the ease of use of vaccines. There are a lot of technologies that are nascent and available now for eliminating cold chain or easier delivery devices. But they're really not being implemented where they need to be in a lot of these products. Is that an issue of providing enough incentives to manufacturers? Are there other ways for getting better implementation? Yeah, actually, you bring up a very good point. I didn't include that, not because I didn't think it was important, because Steve told me I had 23 minutes and 41 seconds, and that was it. So I'm pretty compulsive about staying within my time. But you're bringing up a really very good point. There are many, many. In fact, we at NIAID have a research program that is in fact directed, I say program, I mean a research initiative, as not just getting a new vaccine or improving on vaccines that we have from an effectiveness standpoint, but for adding a degree of practicality to vaccines that we already have, including cold chain issues and others. So we think it's important enough that we're actually making it a research initiative that, and people were surprised at that, saying, well, why would you be interested in that? Because you're interested in it, because if you have a vaccine that you can't implement because of technical constraints, then you really gotta get a vaccine that you can get to the people. So your point is very well taken. Yes. I'm Georgia Sambanaris with USAID. My question deals with cost effectiveness. Given the high cost of vaccine development and the limited budget resources we will have in the future in the foreign aid programs as well as host country counterparts, I'm wondering if you recommend a model such as the UK's National Institute for Health and Clinical Excellence for Assessing Cost Effectiveness Analysis related to vaccine development. Or institutionally, how do you recommend dealing with the cost issues given limited budget resources? Well, from the standpoint of how I look at it, since we do the research development, that's an interesting tension that we have because vaccine development, particularly vaccine trials are very costly. And right now, particularly when you have a flat budget like we've had for the last several years and even looking, if you read the paper, at the possibility of even a cut in our budget, that the tension is between doing fundamental basic research, the typical R01 grant approach. And every time you do an initiative that's a programmatic initiative, vaccine trials cost, as you well know, tens and tens and tens of millions of dollars. People look at that and say, my God, you're talking now about hundreds and hundreds of grants that won't get funded. So what we try and do is to do a delicate balance between maintaining the investigator-initiated approach and actually continuing to make vaccine a high priority. And that's what we've done. Again, I can't speak for implementation because we do the vaccine. We have vaccine programs now in tuberculosis and malaria and in HIV that are really quite expensive. And we're struggling right now, just if you just take HIV as a prototypic example. So we have a successful, albeit modest vaccine that I alluded to the RV-144. We need to follow up on that, not only in Thailand, but also in a different risk region like in Southern Africa. That's very costly. And we made a decision that we are going to pursue that, despite the fact that it's gonna cost a lot of money. So we're, you know, we have partners in that, we have the Billum and the Gates Foundation, we have the Department of Defense, we have a bunch of others. So it's a very difficult decision to make, but the bottom line of what I'm saying is that ultimately vaccines are so cost-effective that the logic tells you that the investment now is gonna pay off. I found it interesting that you really never once mentioned vaccine manufacturers during this talk. What should be the relationship between those of you in NIH and the other governmental organizations and the people who are gonna produce these vaccines? What would be the most productive relationship? You know, it's interesting that you say that. I sort of, like my heart sunk when you say that, it's sort of, I'm so wedded to our collaborations with industry that, you know, I didn't mention my daughter in the talk either, but, and she's a really important part of my life. So I sort of put it in the same category. I apologize for not doing it, but you're absolutely right. Everything we do in vaccine is in a public-private partnership with industry. I mean, I mentioned the RV-144 vaccine. That is a very close collaboration, not only with the NGOs like the Billum and the Gates Foundation, but with Sanofi Pasteur, with Novartis and others. Every vaccine that I mentioned that we're involved with is involved with a pharmaceutical company. So you're absolutely right. I didn't mention it, and I'm not being facetious when I say, because I take it for granted that I didn't mention it. So thank you for bringing that up. Okay, thank you.