HIV vaccine development: Lessons from the past, informing the future

In September 2007, a clinical trial (STEP trial) evaluating the candidate HIV vaccine MRK Ad5 HIV-1 gag/pol/nef from Merck & Co Inc was halted at the first interim analysis because the vaccine demonstrated no positive impact on virus acquisition or virus load following infection. Additionally, there was an increased rate of HIV infection in vaccinees who had prior immunity to adenovirus type 5 (Ad5) and/or were circumcised. This failure of the vaccine, as well as the apparent harm caused to some study participants, generated a massive pessimism regarding HIV vaccine development. Concerns regarding the future of HIV vaccine research led to a summit convened by the NIAID in March 2008 to provide new directions in HIV vaccine research. A shift in emphasis focused on three areas: discovery research, animal models and clinical research. In each of these areas, notable new activities have occurred: a wealth of information has emerged from the STEP trial, promising results have been reported on assay development for markers of vaccine-induced immune function, and evaluations of promising new experimental vaccines have occurred in nonhuman primates. Overall, the progress in the field of HIV vaccine research since September 2007 has reinforced the need for a balanced approach between basic vaccine discovery and development, as well as the importance of addressing questions in nonhuman primate studies and clinical trials. This article discusses how past product failures have invigorated the field of HIV vaccine research by addressing critical questions and suggesting additional possible approaches to follow. As a result of the insight gained, a new sense of optimism exists in the field of HIV vaccine research.