105 Rationale for HIV vaccines design

Development of an effective and safe HIV vaccine presents unique challenges. Despite the progress in understanding the biology of HIV-1 and its recognition by the human immune system, we have not yet developed an efficacious HIV-1 vaccine. During the last years, the results were obtained that has given hope that vaccination may prevent HIV-1 acquisition. The results of post-RV144 correlates and sieve analyses suggest that vaccine worked probably involving an immunological mechanism in the second variable loop (V2). A high resolution structure of the envelope trimer was solved, and this information is being used for the design of new generations of vaccines aimed at inducing protective antibodies. New techniques have facilitated the discovery of new human broadly neutralizing antibodies (BrNAbs) that target and delineate diverse conserved epitopes on the envelope glycoprotein spike. The epitopes of these BrNAbs can serve as templates for immunogen design aimed to induce similar antibodies. A separate goal of HIV vaccine research is to identify the best strategy for immunization and delivery agents. Several vectors and adjuvants have been developed. Significant advances have been made towards the development of tools to assess preclinical efficacy and understanding the correlates of protection in non human primate models. We observe the preventive potential of microbicides, PrEP, and earlier antiretroviral treatment of infected individuals has been demonstrated. All of these interventions may have a significant impact in reducing the incidence of HIV infections. However a safe and efficacious vaccine will be the most efficient way to control global HIV-1 pandemic, and scientific opportunities look promising.