HIV-1 vaccine clinical trials: the Brazilian experience

Although the development of an effective HIV-1 vaccine has proved very challenging for more than two decades, it remains the best hope to control the HIV pandemic. Since Brazil has particular epidemiological features, as well as adequate policies and infrastructure, the country has been an interesting site for HIV vaccine trials. Since 1995, eight trials were performed in Brazil enrolling over 2000 subjects. Peptide vaccine candidates were initially designed to elicit neutralising antibodies as an attempt to provide sterilising immunity against HIV-1. This strategy, however, has proved extremely difficult, and candidates were poorly immunogenic. Therefore, the next vaccine candidates focused mainly on the induction of cell mediated immune responses that would limit AIDS progression and transmission by suppressing viremia. Such candidates were naked DNA or viral vectors in either prophylactic or therapeutic approaches. Even though several candidates were immunogenic, protective immune responses against HIV-1 remain to be achieved. However, several studies with non-human primates and human elite controllers demonstrate that effective immune responses against HIV-1 may be elicited, supporting the belief that an HIV-1 vaccine is possible. Much has been learned, and now the development of an effective HIV-1 vaccine requires resetting priorities with focus on basic research, considering the merits of neutralising antibodies and CMI, as well as the role of innate immunity on HIV-1 protection. In this new perspective, large-scale trials should be replaced by smaller preliminary efficacy studies.