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: 7923783
• 负责人: LINDSAY M. WOHLERS
• 金额: $ 150.59万
• 依托单位: NOVARTIS VACCINES AND DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7923783
• 关键词: Animals; Antibodies; Antibody Avidity; Antibody Formation; Antigens; Appearance; Arts; B-Lymphocytes; Binding; Biological Assay; Blood Cells; CD4 Positive T Lymphocytes; CD8B1 gene; CTL assay; Cell Count; Cell-Mediated Cytolysis; Cells; Characteristics; Clinical Trials; Collaborations; Combined Vaccines; Complement; Cytolysis; Cytotoxic T-Lymphocytes; Data; Development; Disease; Disease Progression; Dose; Drug Formulations; Enzyme-Linked Immunosorbent Assay; Epitopes; Equilibrium; Evaluation; Feedback; Gagging; Goals; Grant; HIV; HIV Infections; HIV vaccine; HIV-1; HIV-1 vaccine; Hand; Human; Immune; Immune response; Immunity; Immunization; Infection; Interferons; Interleukin-10; Interleukin-2; Interleukin-4; Lead; Logistics; Macaca mulatta; Measurement; Mediating; Memory; Memory B-Lymphocyte; Modality; Modeling; Molecular Cloning; Monitor; Oryctolagus cuniculus; Peptides; Peripheral Blood Mononuclear Cell; Phase; Phenotype; Plasma; Primates; Proteins; Research; Resources; SIV; Safety; Side; Signs and Symptoms; Staining method; Stains; Structure; System; T-Lymphocyte; Technology; Testing; Thymidine; Treatment Protocols; Universities; Upper arm; Vaccines; Variant; Viral; Viral Proteins; Viral load measurement; Virus; base; clinical phenotype; cost; cytokine; cytotoxic; enzyme linked immunospot assay; fitness; follow-up; gag Gene Products; immunogenicity; improved; in vivo; killings; long term memory; meetings; neutralizing antibody; nonhuman primate; novel; novel strategies; pre-clinical; pressure; research clinical testing; response; simian human immunodeficiency virus; vaccine candidate; vaccine delivery; vaccine efficacy; vaccine-induced immunity; vector vaccine

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 Env结构， 诱导广泛中和抗体的特定目标。在最后阶段，我们的目标是 将这些与重要的T细胞抗原一起配制成多组分HIV候选疫苗， 诱导对保守病毒表位的多重效应子应答。我们将最终研究 在非人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灵长类动物中评价抗原， 控制HIV感染的效应子反应。我们的具体目标是： 1.评价诱导广泛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HIV体内复制的CTL应答 3.一种能够维持持久B和T细胞反应的有效平衡的T辅助细胞反应。 这个核心（C）将提供后勤和科学资源以及非人类灵长类动物研究 评估不同疫苗成分和输送系统的安全性、体液免疫、 细胞介导的和粘膜读数使用远系杂交的MHC特征的印度恒河猴。此外，委员会认为， 本核心（C）还将通过挑战和随访研究疫苗策略的有效性。 免疫的动物，并将疫苗保护与诱导的免疫应答相关联。这些目标 将采取最有前途的候选人能够持续持久，持久的协同作用， 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 由该核心提供的标准化的现有技术水平的体液、T辅助细胞和CTL测定将提供恒定的 反馈给其他项目和核心，以比较抗原和由 不同的项目。这种标准化的并行分析系统将为 合理选择最好的疫苗成分和初免-加强组合， 项目作为主要的Env抗原出现在小动物研究中。这种理性的方法基于 逐步临床前评估和选择将为临床试验提供最佳疫苗候选物。