The Pursuit of a HIV Vaccine – Trials, Challenges and Strategies

The trademark of a viral vaccine is to elicit robust, effective and extensive immune responses against the virus. One way of demonstrating that antibodies can elicit protection is by passive administration followed by virus challenge in in vivo models. A vaccine capable of eliciting satisfactory levels of antibody against HIV-1 could prevent the establishment of infection. In the case of HIV-1 the development of an effective vaccine has been an elusive one mainly due to the antigenic and genetic diversity of the virus. The first endeavor to produce a protective vaccine against HIV-1 was to generate HIV-1 Envelope (Env)-specific antibody responses using recombinant gp120 antigens indicated that the antibodies failed to neutralize HIV-1 [1]. Two more studies in Phase III efficacy clinical trials revealed the failure of the recombinant gp120 vaccine to prevent HIV-1 infection or reduce viremia [2,3]. Studies following these trials based on eliciting cytotoxic T Cell (CTL) responses against HIV did not show any promise. But lately, the modest efficacy against HIV shown in the RV144 Phase III clinical trial in controlling HIV infection [4] and the isolation of neutralizing antibodies (nAb) called broadly neutralizing antibodies (bnAb) able to neutralize a broad spectrum of HIV-1 variants [5] has generated great optimism in the HIV-1 vaccine research field. In this review we will discuss the existing status of the research efforts focused on the development of an HIV-1 vaccine, lessons learned, challenges to be addressed and current strategies to develop an effective vaccine.