Twenty-five years after its onset, AIDS continues to grow and outpace the global response. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2006 Report on the global AIDS epidemic, worldwide an estimated 38.6 million people are currently living with HIV. The epidemic is particularly worrisome for women and youth: in 2005, 59 per cent of infected people in sub-Saharan Africa were women; HIV-infected young women, aged 15 to 24, outnumbered their male counterparts by three to one. Approximately 6,000 to 7,000 people in that age group contract the virus each day.

The increasing effect of what is generally referred to as the feminization of HIV/AIDS is a phenomenon that can be observed in all regions across the world. Young people are also disproportionately affected, and despite internationally agreed goals to step up prevention efforts, activities to adequately protect them from HIV/AIDS are insufficient. However, there are signs of hope. Infection rates have plateaued in several African countries, but with around 4.1 million new infections annually, there is no room for complacency. The impact of HIV/AIDS is especially serious in the developing world since 95 per cent of new infections occur there. To help prevent HIV/AIDS, the need is evident for a vaccine-a substance that trains the immune system to recognize and protect against a disease or other infectious agent.

Historically, vaccines have been particularly efficient and cost-effective. The introduction of the smallpox vaccine, for example, made it possible to eradicate the disease altogether. They are also good poverty-fighting tools, as they tend to reach the poor and disadvantaged populations better than other health services.

On the minds of a lot of people, however, is the question, "Is it possible to develop an AIDS vaccine?" The answer is yes. Most scientists believe that an effective preventive AIDS vaccine is challenging but feasible. Virtually everybody's immune systems can keep the virus in check for a number of years. However, there are certain individuals that are resistant to HIV infection, such as a group of Kenyan sex workers who, despite repeated exposure to the virus, never contracted HIV. Their bodies somehow are able to control infection. It has also been found that AIDS vaccines can protect monkeys from the simian equivalent of HIV. All these are important, if not yet well understood, clues for the development of an AIDS vaccine. Accordingly, more than 30 vaccine candidates are currently undergoing early trials on four continents.

On the other hand, the challenges for developing an AIDS vaccine are formidable. Scientifically, the human immunodeficiency virus has turned out to be a very elusive target; in fact, HIV is one of the most complicated viruses ever identified, and it targets and destroys the very immune system that a vaccine traditionally triggers. Its genetic hyper-variability is daunting; millions of viruses are constantly produced and their mutation rates are staggering. The immune system is presented with an endless stream of new forms of the virus that it is unable to recognize and control.

In addition, clinical trials to test the safety and efficacy of an AIDS-vaccine candidate are long and costly. A vaccine is developed in laboratories and initially tested in animals, after which it generally has to go through three phases of testing on human beings to be licensed for use (see box below). In 2005, 13 new trials of preventive AIDS-vaccine candidates began in nine countries worldwide, including the developing world, two of them involving Phase II trials. India, China and Rwanda started their first vaccine trials in 2005 and South Africa began Phase II.

Contrary to a common myth that HIV vaccines can cause a person to get HIV or AIDS, it is absolutely not possible for the current HIV-vaccine candidates to cause a person to become infected with HIV, as these vaccines do not contain the virus, but rather only copies of small non-infective parts of the virus, so they cannot cause HIV transmission. Scientific breakthroughs are by nature unpredictable. Given the complexity of developing an AIDS vaccine, it is currently not possible to give a timeframe for its development. Strong and effective action, however, could significantly accelerate the date at which an AIDS vaccine emerges.

The potential impact of the AIDS vaccines, however, would be enormous, especially for the developing world. Simulation modelling studies have investigated the potential impact of HIV/AIDS vaccines in a variety of countries. More than 30 studies have been published in the last ten years, based on data from Eastern and Southern Africa and India. While the results focus on individual countries and are based on specific assumptions, these studies generally find that even vaccines that are only partially effective (30 to 50 per cent) could significantly reduce the number of new infections. A vaccine could be partially effective by protecting either completely a fraction of the population, or everyone in the same way, i.e. by lowering their chances of becoming infected as compared to the situation without a vaccine. In other words, a 50-per-cent effective vaccine could protect half the population completely or lower by 50 per cent everyone's chances of becoming infected.

Using the trends observed in these earlier studies, the International AIDS Vaccine Initiative (IAVI) has produced preliminary estimates of the global impact of an AIDS vaccine. The results are based on three scenarios reflecting different levels of vaccine efficacy and population coverage. These scenarios were combined with long-term projections from UNAIDS on the expected trajectory of the AIDS epidemic over the next 25 years, assuming that existing prevention and treatment programmes continue to grow until 2012, then plateau at 80 per cent coverage.

For purposes of illustration, the simulation assumes that an AIDS vaccine is introduced in 2015 (see graph). These data show that even an imperfect vaccine would cut the number of people infected every year by more than half. According to the IAVI model, if a 60-per-cent effective vaccine becomes available in 2015 and is given to a third of the population in developing countries, the rate of infection by 2030 would be 4.7 million a year, instead of 10 million, and over 45 million people who would otherwise become HIV positive from 2015 to 2030 would be protected. In a more optimistic scenario, a very effective vaccine that reaches a larger sector of the population could substantially reverse the spread of the epidemic. The model also estimates that a 95-per-cent effective vaccine given to 40 per cent of the population could reduce by 82 per cent the number of people infected every year, and over 70 million people would be protected. Even a less effective vaccine reaching fewer people would help stop the epidemic. A 40-per-cent effective vaccine given to a fifth of the population could still reduce the annual number of new infections by about a third, preventing nearly 30 million of the 150 million new infections that would otherwise be expected over a 15-year period.

To realize the great potential that AIDS vaccines hold, it is crucial to overcome various challenges on the road ahead, among them funding issues and the creation of incentives to increase private-sector research and development for AIDS vaccines. Most vaccine development expertise rests in private-sector vaccine companies, which traditionally play a leading role in translating important basic research into vaccines that can be manufactured for commercial use. However, there is little incentive for private companies to invest in their AIDS vaccines, research and development, as the largest demand will be in developing countries least able to pay. According to a report on Tracking Funding for Preventive HIV Vaccine Research & Development, published jointly by IAVI, the AIDS Vaccine Advocacy Coalition, the Alliance for Microbicides and UNAIDS in June 2005, the public sector accounted for 88 per cent, the private sector only 10 per cent and the philanthropic sector 2 per cent of the total $682 million spent on AIDS vaccine research and development in 2004. Possible incentives for the private sector could be government tax credits or market guarantees, the so-called "advance market commitments", which are pre-commitments by donors to buy an effective vaccine at a pre-specified price, if and when it is actually developed.

There is also a need for increased and sustained funding for AIDS vaccine research and development to speed eventual success. The overall funding gap for vaccines is estimated at about $300 million to $400 million annually; IAVI has called for a closing of this gap by 2008. Ultimately, in order to expand and sustain the global response to HIV/AIDS, a long-term and comprehensive approach is needed, combining increased use of existing prevention methods with new preventive technologies, particularly vaccines and microbicides. The importance of these technologies was strongly reiterated in the recent UN High-level Meeting on AIDS, held from 31 May to 2 June 2006 in New York. The meeting's Political Declaration states, in the context of a comprehensive response to HIV/AIDS, the need to "develop with equal urgency better tools-drugs, diagnostics and prevention technologies, including vaccines and microbicides-for the future".

The impact of AIDS vaccines could be particularly significant for women and young people. Ideally, women would be able to use a vaccine without their partner's knowledge, providing them with a powerful HIV-prevention option. Adolescents, especially girls, who are particularly vulnerable to infection, could be vaccinated at pre-adolescence, before the onset of sexual activity or other potentially high-risk behaviours. To achieve the dream of a world without AIDS, vaccines remain humanity's best hope.