Scientific Project 2: HIV AIDS Defining molecular signatures in humans following vaccination that can inform pathways to protective immunity against HIV-1 infection

科学项目 2：HIV AIDS 定义人类接种疫苗后的分子特征，为针对 HIV-1 感染的保护性免疫途径提供信息

• 批准号: 10631105
• 负责人: Margaret Juliana McElrath
• 金额: $ 13.48万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-19 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631105
• 关键词: 2019-nCoV; AIDS prevention; Acceleration; Acquired Immunodeficiency Syndrome; Active Immunization; Adjuvant; Africa; Antibodies; Antibody-mediated protection; Antigenic Specificity; Antigens; Architecture; Area; B cell repertoire; B-Lymphocytes; Benchmarking; Biological Assay; Bone Marrow; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cell physiology; Cells; Circulation; Data Sources; Development; Epidemic; Epitopes; Evaluation; Evolution; Formulation; Generations; Goals; HIV; HIV Infections; HIV Vaccine Trials Network; HIV vaccine; HIV-1; HIV/AIDS; Helper-Inducer T-Lymphocyte; Human; Immune; Immune response; Immunity; Immunization; Infection; Innate Immune Response; Investigation; Knowledge; Libraries; Malaria; Measures; Metadata; Molecular; Molecular Profiling; Participant; Pathway interactions; Peripheral; Phase; Phenotype; Placebos; Plasma Cells; Population; Population Heterogeneity; Prevention; Preventive; Proteomics; Protocols documentation; Regimen; SARS-CoV-2 infection; Safety; Serology; Source; System; T cell receptor repertoire sequencing; T cell response; T-Cell Immunologic Specificity; T-Cell Receptor; T-Lymphocyte; Technology; Testing; Tissues; Translating; Vaccination; Vaccine Design; Vaccines; Viral; adaptive immune response; analytical tool; draining lymph node; efficacy trial; in vivo; insight; lymph nodes; multimodality; neutralizing antibody; novel; polyclonal antibody; prevent; primary endpoint; response; study population; success; vaccine efficacy; vaccine trial

The overall goal of HIPC3 Project 2 is to identify human molecular signatures induced by HIV-1 vaccines and adjuvant formulations that are of potential relevance to protection against HIV-1 infection in diverse populations. Our proposed investigations will focus on three areas where critical insights are needed: 1) comprehensive assessment and comparison of the quality and enhanced potency and durability of immune responses following immunization with a soluble native-like Env trimer formulated with different adjuvants, 2) evaluation of lymph node germinal cell activities and B cell function and phenotype that have the potential to initiate development of HIV-1 broad neutralizing antibodies, and 3) advance high-throughput systems to interrogate the HIV-specific T cell repertoire following vaccination and identify profiles that may associate with immune protection in partially efficacious vaccine trials. Embedded in these studies will be selected analyses of response signatures in unique tissue sources and in diverse populations. These investigations will accelerate progress toward an effective vaccine by probing innate and adaptive immune responses at an unprecedented level in humans.

HIPC3项目2的总体目标是确定HIV-1诱导的人分子特征 与保护HIV-1有关的疫苗和辅助配方 不同人群的感染。我们提议的调查将重点放在三个领域 需要关键见解：1）质量的全面评估和比较 免疫后免疫反应的效力和耐用性增强 用不同的佐剂配制的天然类似Env三聚体，2）评估淋巴结生发的评估 细胞活动以及B细胞功能和表型，具有发育的潜力 HIV-1广泛中和抗体，3）提前高通量系统来询问 疫苗接种后HIV特异性的T细胞库，并确定可能与 部分有效的疫苗试验中的免疫保护。这些研究嵌入了 在独特的组织来源和不同种群中的响应特征的选定分析。 这些调查将通过探测先天和 在人类空前的自适应免疫反应。