History of AIDS Vaccine Efforts

AIDS researchers who first attempted to develop a vaccine against HIV, beginning in the late 1980s, sought to develop one that would work primarily by eliciting an antibody response—which is how most existing vaccines are throught to work. These scientists re-created a part of HIV called the virus envelope protein and used it as an antigen in their vaccine candidate and combined it with an adjuvant, hoping their vaccine candidate would elicit neutralizing antibodies against HIV. Next, they assessed this vaccine candidate's safety and ability to provoke an immune response in animal studies, and then tested it on volunteers in a series of closely monitored clinical trials.

Purified antigens have been used to make vaccines against hepatitis B and the human papillomavirus, and the approach is increasingly popular in modern vaccinology. But because HIV mutates rapidly and its outer spike protein conceals itself from the immune system, creating the appropriate viral antigens to use in a vaccine proved remarkably difficult. It was clear by the late-1990s that the approach—at least as initially conceived—would not work with HIV.

AIDS vaccine researchers then turned to harnessing the other arm of the adaptive immune response: cell-mediated immunity. This response dispatches T cells to destroy cells in the body that have already been infected by viruses. T cells can also release substances that inhibit HIV from replicating and spreading through the body.

It was not clear that vaccines devised to stimulate this response would block HIV infection or whether they’d only suppress existing infections. But researchers, encouraged by the results of animal studies, pressed ahead. Today, there are around 30 AIDS vaccine candidates in the clinical pipeline and nearly all are devised to elicit CMI responses. Yet the performance of CMI-based vaccines has so far been disappointing. Most notably, the failure in 2007 of a CMI candidate considered by many at the time to be the most promising in the AIDS vaccine pipeline was a disappointment to AIDS vaccine researchers.

That candidate's failure reinforced a consensus that has grown in the field over recent years that the development of an effective AIDS vaccine requires a renewed focus on the molecular details of HIV infection and the immune system’s response to it. Further, many scientists, including those at IAVI, have come to believe that an AIDS vaccine candidate will provide robust protection against HIV infection only if it is devised to engage both cell-mediated and antibody-based immune responses.

In response to the challenge, in recent years many organizations dedicated to AIDS vaccine development have renewed their focus on collaborative HIV research aimed at designing a new generation of investigational vaccines. For example, the US National Institute of Allergy and Infectious Diseases launched its Center for HIV/AIDS Vaccine Immunology in 2005; the Bill & Melinda Gates Foundation in 2006 introduced the Collaboration for AIDS Vaccine Discovery and has provided support to the Global HIV Vaccine Enterprise. IAVI too has been at the forefront of this movement. We have launched three international vaccine discovery consortia to tackle some of the most pressing scientific challenges facing AIDS vaccine developers, established new laboratories and linked HIV studies conducted by developing country researchers to vaccine development efforts worldwide.