The long-term objective is to develop HIV vaccines capable of protecting humans against HIV infection anddisease. Within the 5 years of this project, our aim is to develop and evaluate new HIV-1 Env structures withthe specific goal of inducing broad neutralising antibodies. Subsequently, in the last phase, we aim toformulate these with important T-cell antigens for a multi-component HIV vaccine candidate capable ofinducing multiple effector responses to conserved viral epitopes. We will ultimately investigate the efficacy ofcandidate vaccines in a non-human primate challenge model. In this core, the immunogenicity of severalantigens will be evaluated in non-human primates using different delivery modalities to induce the multipleeffector responses which control HIV infection.
Our specific aims are:1. To evaluate novel strategies to induce broad high titer neutralizing antibodies2. CTL responses able to kill HIV infected cells and/or suppress HIV replication in vivo3. A potent balanced T-helper response capable of sustaining durable B as well as T-cell responses.This core (C) will provide the logistics and scientific resources as well as the non-human primate researchexpertise to evaluate the different vaccine components and delivery systems with regard to safety, humoral,cell-mediated and mucosal readouts using outbred MHC characterized Indian rhesus macaques. Moreover,this core (C) will also investigate the efficacy of the vaccine strategies by challenge and follow-up of theimmunized animals and correlate vaccine protection with the immune responses induced. These objectiveswill be met by taking the most promising candidates capable of sustaining durable, long-lasting synergisticimmune responses. The correlates of immunity observed during the course of this project will guide theselection of the combined vaccine and delivery systems to be used in year 4/5. In addition, data derived fromstandardized state of the art humoral, T-helper and CTL assays provided by this core will provide constantfeedback to other projects and cores for the comparison of antigens and delivery systems provided by thedifferent projects. This system of standardized side by side analysis will provide an unbiased basis for therational selection of the best vaccine components and prime-boost combinations from each of the differentprojects as the lead Env antigens emerge from small animal studies. This rational approach based onstepwise pre-clinical evaluation and selection will provide optimal vaccine candidate(s) for clinical trials.
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