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 疾病。在该项目的 5 年内，我们的目标是开发和评估新的 HIV-1 包膜结构 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 将这些与重要的 T 细胞抗原一起配制为多组分 HIV 候选疫苗，能够 诱导对保守病毒表位的多重效应反应。我们将最终研究其功效 非人类灵长类动物攻击模型中的候选疫苗。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 感染的效应反应。我们的具体目标是： 1. 评估诱导广泛高效价中和抗体的新策略 2. CTL反应能够杀死HIV感染细胞和/或抑制HIV体内复制 3. 有效平衡的 T 辅助反应，能够维持持久的 B 细胞和 T 细胞反应。 该核心（C）将提供后勤和科学资源以及非人类灵长类动物研究 评估不同疫苗成分和递送系统的安全性、体液性、 使用远交 MHC 的细胞介导和粘膜读数表征了印度恒河猴。而且， 该核心（C）还将通过挑战和后续行动来调查疫苗策略的有效性 免疫动物并将疫苗保护与诱导的免疫反应联系起来。这些目标 将通过选择能够维持持久、长期协同作用的最有前途的候选人来满足 免疫反应。在本项目过程中观察到的免疫相关性将指导 选择第 4/5 年使用的联合疫苗和输送系统。此外，数据来源于 该核心提供的标准化最先进的体液、T 辅助细胞和 CTL 检测将提供恒定的 向其他项目和核心提供反馈，以比较由 不同的项目。这种标准化并排分析系统将为以下方面提供公正的基础： 从每种不同的疫苗中合理选择最佳的疫苗成分和初免-加强组合 作为主要包膜抗原的项目是从小动物研究中出现的。这种理性的方法基于 逐步的临床前评估和选择将为临床试验提供最佳的候选疫苗。