Professeur honoraire à l’Université Paris 7-Denis Diderot, 39 rue Seignemartin, 69008 Lyon, DR2 CNRS, Unité Inserm U503, IFR 128, CERVI, 21 av. Tony-Garnier, 69007 Lyon
Some 50 phase I clinical trials of candidate vaccines against HIV/AIDS, 2 phase II trials and 2 phase III trials have been completed since the 1980s, altogether involving more than 16,000 volunteers. Although several neutralization epitopes have been identified on the surface of the virus glycoprotein spikes, the design of an envelope-based HIV vaccine capable of eliciting broadly reactive neutralizing antibodies remains as an elusive goal. A gp120-based vaccine, which was tested in two phase III trials, one in the USA and the other in Thailand, was found to be devoid of protective efficacy. The observation was made in the monkey model, using the simian immunodeficiency virus (SIV), that both virus loads and the clinical evolution of the disease were controlled by the CD8+ T-cell response (CTL) of the animals. This has prompted the development of vaccine candidates capable of inducing HIV-specific T-cell responses. A series of HIV vaccines based on live virus vectors already are in clinical studies, including a live recombinant canarypox virus vaccine (ALVAC), which is in phase III in Thailand, a non-replicative adenovirus type 5 (Ad5) vaccine, which has entered phase II clinical trials in the USA and The Caribbeans, and live recombinant vaccines based on the attenuated vaccinia virus MVA vector, which already have been through several phase I/II studies. These live recombinant vaccines have been evaluated either alone or as booster immunizations after priming with DNA vaccines. A whole array of other vaccines based on live vector vaccines, pseudoviral particles, peptides and other designs, have been tested in nonhuman primate models. So far, using the macaque/SIV model, none of the available vaccine candidates has been able to prevent infection following experimental challenge of the animals, but the vaccinated animals showed significant reduction of viral loads as compared to controls and were able to maintain their CD4+ T-cell count. T-cell stimulating vaccines thus illustrate a new paradigm in vaccinology, that of vaccines which are unable to prevent infection, but can prevent the occurrence of disease or at least slow down its evolution through continuous control of virus replication in the vaccinated host. The efficacy of these vaccines in humans now remains to be established.