February 15, 2008 – At the annual conference of the American Association for the Advancement of Science, the organization’s president, eminent scientist and Nobel laureate David Baltimore, commented on February 14 in Boston on the current state of AIDS vaccine research. Professor Baltimore expressed concern at the field’s lack of success so far in developing an effective AIDS vaccine but emphasized that researchers must continue to move ahead given how crucial it is to develop such a vaccine. The UK media reported heavily on his remarks; many of the headlines were pessimistic about the prospects for developing an AIDS vaccine.
The International AIDS Vaccine Initiative (IAVI) agrees with Professor Baltimore that the search for a vaccine is vital. Since HIV was identified as the virus responsible for AIDS 25 years ago, researchers have made considerable progress understanding the virus and human responses to it. In response to these news reports, IAVI issued the following statement to provide an overview of the broad spectrum of scientific evidence from human studies of HIV infection and animal models to support the belief that an AIDS vaccine is possible. The evidence includes:
1) The experience of elite controllers. An important fact is that almost everyone who becomes infected with HIV manages to control the virus for many years without the need for antiretroviral drugs. At the extreme, there are clearly documented cases of individuals who have been infected for 25 years or more and have shown no ill effects. Called elite controllers or long-term non-progressors, at least some of these individuals control their HIV infection by means of their immune system. If scientists can work out the type of immune responses that afford the elite controllers protection, then the hope is that researchers can replicate those with a vaccine.
2) The experience of highly exposed uninfected individuals. There are also documented cases of individuals who have been repeatedly exposed to HIV but have not become infected. These individuals, known as the highly exposed uninfected, were first described among commercial sex workers in Nairobi, Kenya. These women remained free of HIV infection despite repeated exposure to HIV from infected partners, suggesting they have immunity to HIV. Again, if scientists can define precisely how these individuals manage to be resistant to HIV infection, it might provide vital clues about how to create a vaccine.
3) The success of live-attenuated vaccines in non-human primates. Research on non-human primates (NHPs) provides further evidence that a preventive HIV vaccine is possible. Some NHPs injected with a vaccine made from live-attenuated SIV, the simian equivalent of HIV, and then challenged with SIV do not become infected. They are protected by the vaccine. The overwhelming majority of non-human primates immunized with live-attenuated SIV significantly suppress the replication of the virus, thus slowing or blocking progression to disease. It is not considered safe to make vaccines for humans using the same approach, that is, using live-attenuated HIV. But by studying how this model works in non-human primates, our closest relatives, the AIDS vaccine field can gain clues about how to make a safe vaccine for humans. IAVI’s Live Attenuated Consortium, which brings together world-class scientists from a variety of institutions, is devoted to this issue.
4) The promise of broadly neutralizing antibodies. AIDS vaccine experts also know that some individuals who are HIV infected produce broadly neutralizing antibodies. These are antibodies that will destroy the vast majority of types of HIV circulating in the world today. In animal experiments, scientists have injected high doses of these human antibodies into non-human primates and found that this injection prevents infection from a challenge. So if researchers can figure out how to design a vaccine that would teach the body to make broadly neutralizing antibodies, there is hope we can design an effective AIDS vaccine for humans. IAVI’s Neutralizing Antibody Consortium is focused on this subject.
Through these consortia and through other efforts, AIDS vaccine researchers today are aggressively working to develop a new generation of vaccine candidates with capabilities that go beyond those currently in testing. Experts are trying to develop candidates that elicit different immune responses from those currently in clinical trials. This includes research on new vectors that replicate in the gut and those that stimulate immune responses at blood and mucosal surfaces where HIV enters the body.
Innovation is a must. To that end, IAVI, with support from the Bill and Melinda Gates Foundation, last year launched a program to identify and evaluate pioneering ideas from outside the AIDS vaccine field that could deliver the breakthroughs that are necessary to move the field forward.
Scientists don’t know how long it will take to develop an AIDS vaccine. We do know from history that a vaccine is the only way to end a major viral epidemic and that perseverance and long-term investment are necessary to develop a vaccine. A robust AIDS vaccine effort has only been underway for the last decade and only two vaccine candidates have been advanced all the way through to efficacy testing.
The world can’t afford not to develop a vaccine. The costs of providing life-prolonging treatment will continue to escalate. UNAIDS projected in September that the pricetag of universal access to AIDS prevention, treatment and care would be roughly $42 billion a year by 2010. Since then UNAIDS has revised its epidemiological figures downwards, but even with a 20 percent cost reduction, spending on AIDS would have to go from a tenth to a quarter of all overseas development assistance to meet the goal of universal access, crowding out other priorities like basic health care, clean water and education.
It is certainly true that developing an AIDS vaccine has proven more difficult than researchers imagined when they first set out on the mission decades ago. But nobody entered this field thinking this was easy work. On the other hand, every researcher involved knew it was vital, and it remains more so today than anyone could have imagined 25 years ago.