Evaluation of HIV-1 Vaccine Candidates in Macaca mulatta

长期目标是开发能够保护人类免受艾滋病毒感染的艾滋病毒疫苗，并 疾病。在这个项目的5年内，我们的目标是开发和评估新的HIV-1环境结构，包括 诱导广泛中和抗体的具体目标。因此，在最后阶段，我们的目标是 将这些与重要的T细胞抗原一起用于多组分HIV候选疫苗 诱导对保守的病毒表位的多个效应器反应。我们将最终调查这种药物的疗效 非人灵长类挑战模型中的候选疫苗。在这个核心中，几种疫苗的免疫原性 将在非人类灵长类动物中使用不同的递送方式来评估抗原，以诱导多个 控制HIV感染的效应器反应。我们的具体目标是： 1.评估诱导广谱高滴度中和抗体的新策略 2.能够杀死HIV感染细胞和/或抑制体内HIV复制的CTL反应 3.一种有效的平衡的T辅助反应，能够维持持久的B细胞和T细胞反应。 这个核心(C)将提供后勤和科学资源以及非人类灵长类研究 评估不同疫苗成分和递送系统的安全、体液、 使用近交系MHC的细胞介导和粘膜读数是印度猕猴的特征。此外， 这一核心(C)还将通过挑战和跟踪调查疫苗战略的效力 免疫动物，并将疫苗保护与诱导的免疫反应相关联。这些目标 将通过选择最有希望的候选人来满足，这些候选人能够保持持久、持久的协同 免疫反应。在本项目过程中观察到的免疫相关性将指导 选择将在第4/5学年使用的联合疫苗和递送系统。此外，数据来源于 由该核心提供的标准化的体液、T辅助细胞和CTL分析将提供持续的 向其他项目和核心提供反馈，以便比较 不同的项目。这一标准化的并列分析系统将为 从每种不同的疫苗中合理选择最佳疫苗成分和最佳强化组合 作为主要环境抗原的项目是从小动物研究中产生的。这种理性的方法基于 循序渐进的临床前评价和筛选将为临床试验提供最佳候选疫苗(S)。

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