[The quest for an HIV vaccine]

At least 49 phase I trials of candidate vaccines for HIV/AIDS, together with two phase II trials and two phase III trials have been completed since the mid 1980s, involving more than 35 different vaccine formulations, 14 different adjuvants and more than 12000 volunteers. Although several neutralizing epitopes have been identified on the surface of the virus glycoprotein spikes, the goal of an HIV envelope-based vaccine capable of eliciting broadly reactive neutralizing antibodies is elusive. A gp120-based vaccine, which was tested in two phase III trials (one in the USA and the other in Thailand), was found to have no protective efficacy when injected every 6 months. The observation that, in the monkey model, both viremia (virus load) and clinical outcome are controlled by the CD8+ T cell response, prompted the development of an array of candidate vaccines capable of inducing HIV-specific T cell responses. A series of HIV vaccines based on live virus vectors are already undergoing clinical studies, including a live recombinant canarypox virus vaccine (ALVAC), which is in phase III trials in Thailand, a non-replicative adenovirus type 5 (Ad5) vaccine, which is entering a phase II trial in the USA and the Caribbean, and live recombinant vaccines based on the attenuated vaccinia virus MVA vector, which have already completed several phase I studies, used either alone or combined with DNA vaccine priming. A whole array of other vaccines based on live vectors, DNA, peptides and other designs, are being tested in nonhuman primates. None of these vaccines has been able to prevent infection following experimental challenge, but all were found to control viral load and to prevent CD4 cell loss. T cell-stimulating vaccines are thus unable to prevent infection but prevent or slow disease progression by controlling virus replication. Their efficacy in humans remains to be determined.