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: 8130717
• 负责人: LINDSAY M. WOHLERS
• 金额: $ 165.97万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8130717
• 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; Regimen; Research; Resources; SIV; Safety; Side; Signs and Symptoms; Staining method; Stains; Structure; System; T cell response; T-Lymphocyte; Technology; Testing; Thymidine; Universities; Vaccines; Variant; Viral; Viral Proteins; Viral load measurement; Virus; arm; 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和感染的艾滋病毒疫苗