Evaluation of HIV-1 Vaccine Candidates in Macaca mulatta

Novartis Vaccines And Diagnostics, Inc., Cambridge MA

Investigators

Linked publications & trials

Abstract

The long-term objective is to develop HIV vaccines capable of protecting humans against HIV infection and[unreadable] disease. Within the 5 years of this project, our aim is to develop and evaluate new HIV-1 Env structures with[unreadable] the specific goal of inducing broad neutralising antibodies. Subsequently, in the last phase, we aim to[unreadable] formulate these with important T-cell antigens for a multi-component HIV vaccine candidate capable of[unreadable] inducing multiple effector responses to conserved viral epitopes. We will ultimately investigate the efficacy of[unreadable] candidate vaccines in a non-human primate challenge model. In this core, the immunogenicity of several[unreadable] antigens will be evaluated in non-human primates using different delivery modalities to induce the multiple[unreadable] effector responses which control HIV infection. Our specific aims are:[unreadable] 1. To evaluate novel strategies to induce broad high titer neutralizing antibodies[unreadable] 2. CTL responses able to kill HIV infected cells and/or suppress HIV replication in vivo[unreadable] 3. A potent balanced T-helper response capable of sustaining durable B as well as T-cell responses.[unreadable] This core (C) will provide the logistics and scientific resources as well as the non-human primate research[unreadable] expertise to evaluate the different vaccine components and delivery systems with regard to safety, humoral,[unreadable] cell-mediated and mucosal readouts using outbred MHC characterized Indian rhesus macaques. Moreover,[unreadable] this core (C) will also investigate the efficacy of the vaccine strategies by challenge and follow-up of the[unreadable] immunized animals and correlate vaccine protection with the immune responses induced. These objectives[unreadable] will be met by taking the most promising candidates capable of sustaining durable, long-lasting synergistic[unreadable] immune responses. The correlates of immunity observed during the course of this project will guide the[unreadable] selection of the combined vaccine and delivery systems to be used in year 4/5. In addition, data derived from[unreadable] standardized state of the art humoral, T-helper and CTL assays provided by this core will provide constant[unreadable] feedback to other projects and cores for the comparison of antigens and delivery systems provided by the[unreadable] different projects. This system of standardized side by side analysis will provide an unbiased basis for the[unreadable] rational selection of the best vaccine components and prime-boost combinations from each of the different[unreadable] projects as the lead Env antigens emerge from small animal studies. This rational approach based on[unreadable] stepwise pre-clinical evaluation and selection will provide optimal vaccine candidate(s) for clinical trials.