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: 10419585
• 负责人: Margaret Juliana McElrath
• 金额: $ 20.45万
• 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/10419585
• 关键词: 2019-nCoV; AIDS prevention; Acquired Immunodeficiency Syndrome; Active Immunization; Adjuvant; Africa; Antibodies; Antibody-mediated protection; Antigenic Specificity; Antigens; Architecture; Area; B cell repertoire; B-Lymphocytes; Benchmarking; Biological Assay; Blood Circulation; Bone Marrow; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Cell physiology; Cells; Data Sources; Development; Epidemic; Epitopes; Evaluation; Evolution; Formulation; Generations; Goals; HIV; HIV Infections; HIV vaccine; HIV-1; Helper-Inducer T-Lymphocyte; Human; Immune; Immune response; Immunity; Immunization; Infection; 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的总体目标是识别HIV-1诱导的人类分子特征 可能与预防艾滋病毒-1相关的疫苗和佐剂制剂 在不同的人群中感染。我们建议的调查将集中在以下三个领域 需要关键洞察力：1)全面评估和比较质量和 可溶性AFP免疫后免疫应答的效力和持久性增强 用不同佐剂配制的类天然Env三聚体，2)淋巴结生发的评价 细胞活性和B细胞功能及表型有可能启动 HIV-1广泛的中和抗体，以及3)先进的高通量系统来询问 接种疫苗后的HIV特异性T细胞谱系和识别可能与 部分有效疫苗试验中的免疫保护。将在这些研究中嵌入 对独特组织来源和不同人群中的反应特征进行精选分析。 这些研究将通过探测天生的和 人类的适应性免疫反应达到了前所未有的水平。