Evaluation of HIV-1 Vaccine Candidates in Macaca mulatta

HIV-1 候选疫苗在猕猴中的评价

• 批准号: 7166863
• 负责人: LINDSAY M. WOHLERS
• 金额: $ 73.11万
• 依托单位: NOVARTIS VACCINES AND DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7166863
• 关键词: AIDS vaccines; B lymphocyte; HIV envelope protein; Macaca; antibody titering; antigen antibody reaction; biomedical facility; clinical research; cytotoxic T lymphocyte; helper T lymphocyte; immune response; immunoregulation; major histocompatibility complex; neutralizing antibody; transfection /expression vector; vaccine development; vaccine evaluation; vector vaccine; virus load; virus replication

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.

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和 疾病。在该项目的5年内，我们的目标是与 诱导广泛中和抗体的具体目标。随后，在最后阶段，我们的目标是 用重要的T细胞抗原制定这些抗原 诱导对保守病毒表位的多个效应子响应。我们最终将调查 非人类灵长类动物挑战模型中的候选疫苗。在这个核心中，几种免疫原性 将使用不同的递送方式在非人类灵长类动物中评估抗原，以诱导多种 控制HIV感染的效应子反应。我们的具体目的是： 1。评估新的策略以诱导广泛的高滴度中和抗体 2。能够杀死艾滋病毒感染细胞和/或在体内抑制艾滋病毒复制的CTL响应 3。能够维持耐用B和T细胞响应的有效平衡T-助力响应。 该核心（C）将提供物流和科学资源以及非人类灵长类动物研究 专业知识以评估有关安全性，体液， 细胞介导的粘膜读数使用MHC的特征是印度恒河猕猴。而且， 该核心（c）还将通过挑战和随访调查疫苗策略的功效 免疫动物并将疫苗保护与诱导的免疫反应相关。这些目标 将获得能够维持耐用，持久协同作用的最有前途的候选人来实现 免疫反应。在本项目过程中观察到的免疫力的相关性将指导 选择将在4/5年使用的组合疫苗和输送系统。此外，来自 该核心提供的标准化最先进的体液，T馆和CTL分析将提供恒定 对其他项目和核心的反馈，以比较由 不同的项目。这种标准化并排分析系统将为 从各个不同 随着小型动物研究的出现，项目的项目。这种理性的方法基于 逐步进行临床前评估和选择将为临床试验提供最佳的疫苗候选者。