Is an AIDS Vaccine Possible?

In the early eighties, when human immunodeficiency virus (HIV) was established as the cause of acquired immune deficiency syndrome (AIDS), there was considerable expectation that a vaccine would soon be developed. However, the scientific community quickly found out that it was confronting an unusually difficult adversary. Although much has been learned about HIV and AIDS, the quest for an effective HIV vaccine is being challenged by a couple of scientific stumbling blocks: we still need to identify the best ways of utilizing vaccines to teach the immune system to fight HIV and AIDS, and at the same time explore ways of addressing the extreme genetic variability of the virus.

People infected with HIV develop antibodies and other immune responses against the virus, but these are not sufficient to eliminate the infection or prevent progression to disease. Consequently, an HIV vaccine will have to "improve on nature", perhaps inducing protective immune responses that would otherwise not take place in someone infected with HIV. The genetic variability of the virus has resulted in different "sub-types" (known by the letters A to J) that are geographically distinct. For instance, sub-type B viruses are commonly found in the Americas and Western Europe, while C and A are more prevalent in Africa. Presently, we do not have sufficient information to know whether a vaccine based on North American viruses would work in Africa, or whether we need to develop a separate vaccine for each HIV sub-type. Despite these inherent challenges, there are several reasons for optimism. Different types of experimental vaccines have been shown to partially protect monkeys and chimpanzees against challenges w ith pathogenic viruses, although we still do not know how relevant these animal experiments are in terms of vaccine-induced protection in humans. This question can only be answered following vaccine trials conducted in healthy human volunteers.

The first such HIV-vaccine trial was conducted in 1987 in the United States. Since then, over 30 prospective vaccines have been tested in human volunteers in small-scale trials (Phase I/II trials). Over 6,000 volunteers have lent their participation to these efforts--most of these have been conducted in the United States and Europe, and the rest in Brazil, China, Cuba, Thailand and Uganda. Phase I/II trials have shown that candidate vaccines are safe and that at least some of them induce immune responses that could protect against HIV infection or AIDS.

However, the only way to know if a vaccine protects against HIV/AIDS is by conducting large-scale Phase III efficacy trials involving thousands of volunteers.

These are extremely complex from the scientific, ethical and logistical standpoint, but they represent an obligatory step in the development of HIV vaccines. The first Phase III trials commenced in the United States in 1998 and in Thailand in 1999, with the participation of a total of 8,000 uninfected volunteers. The candidate vaccines for the trials were produced by VaxGen, a California-based company, using HIV strains locally prevalent in these countries. The initial results of the Phase III trials will be available within the next two years and will present our first real opportunity of knowing if we are on the right track to producing a vaccine. The second Phase III trial, using a combination of two candidate vaccines, is in the planning stages at the National Institutes of Health in the United States and could begin within the next two years. In addition, there is a new generation of candidate vaccines under development, soon to move to small-scale trials in human volunteers. The best of these candidate vaccines will be selected for Phase III trials.

As the HIV/AIDS epidemic continues to exact its punishing toll, the need to intensify our efforts to find an effective vaccine is greater than ever. There is a broad consensus that the best way to accelerate the development of an AIDS vaccine is by conducting multiple vaccine trials simultaneously in industrialized and developing countries. Multiple trials are essential to evaluate different types of vaccines against different sub-types. If the quest for this elusive vaccine appears futile, then we should share the blame with our adversary. We have yet to bring the same sense of urgency to the vaccine quest as we have to our pursuit of anti-HIV drugs. This is demonstrated, at least in financial terms, when we note that globally, only $300 million were invested in HIV-vaccine research in 1999, which amount to a mere fraction of the $3 billion that are annually spent on anti-HIV Arugs in the United States and Europe.

Investment in anti-HIV drugs is welcome and essential. Still, the extreme imbalance needs to be set right with a sense of urgency, as an effective vaccine can herald substantial long-term benefits to societies and economies. A serious HIV-vaccine effort will require additional funding to promote the development of new vaccines for testing and to strengthen sites in developing countries where candidate vaccines will be tested and ultimately deployed. If the international community realizes that an HIV vaccine is one of the best examples of what we term "a global public good", and assumes responsibility to support its development with an urgent sense of commitment, only then will the quest for an AIDS vaccine be closer to fruition.

Dr. Jose Esparza is Coordinator of the HIV Vaccine Initiative, jointly sponsored by the World Health Organization and the Joint UN Programme on HIV/AIDS (UNAIDS).