Core B: Non-human Primate Core

核心B：非人类灵长类核心

• 批准号: 10731278
• 负责人: Kristina De Paris
• 金额: $ 45.83万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10731278
• 关键词: 1 year old; Address; Adherence; Adjuvant; Adolescent; Adult; Animals; Antibodies; Authorization documentation; B cell differentiation; B-Lymphocytes; Binding Sites; Biological Assay; Biological Factors; Biological Products; Breeding; California; Cell Lineage; Child; Childhood; Clinical; Clinical Data; Collaborations; Communicable Diseases; Communication; Databases; Decision Making; Dedications; Development; Electronic Mail; Emulsions; Ensure; Epidemic; Foundations; Goals; HIV; HIV envelope protein; HIV vaccine; HIV/AIDS; Health; Housing; Human; IACUC; Immune; Immune system; Immunity; Immunization; Immunize; Infant; Infection; Infrastructure; Knowledge; Lead; Macaca; Macaca mulatta; Maintenance; Mission; Modeling; Molecular; Monitor; Nature; Observational Study; Paris, France; Partner in relationship; Pathway interactions; Pregnancy; Primates; Procedures; Productivity; Progress Reports; Regimen; Regulation; Research; Research Project Grants; Resources; Role; Sampling; Services; Systems Biology; Time; Translational Research; Update; Vaccinee; Vaccines; authority; experience; experimental study; genetic signature; gut microbiome; human disease; human model; meetings; microbiome; neutralizing antibody; nonhuman primate; pathogen; procedure safety; programs; sample collection; symposium; vaccine delivery; vaccine strategy

ABSTRACT – Nonhuman Primate Core (Core B) The end of the HIV/AIDS epidemic will be achievable only when an effective vaccine regimen can achieve long- term protective immunity, similar to that of vaccines that have nearly eliminated other global pathogens. The induction of broadly neutralizing antibodies (bnAbs) against the HIV envelope (Env) is considered vital for an effective HIV vaccine. Yet, despite the delineation of the coevolution of Env-specific antibodies and their cognate Env intermediates from the germline BCR to bnAbs, few HIV vaccine strategies have been successful in eliciting HIV Env Abs with broad heterologous neutralization capacity. Our knowledge about critical factors influencing B cell differentiation and lineage commitment remains limited. The proposed research is built on a foundation of prior research observations on the development of bnAbs in ~ 50-60% of infant and adult rhesus macaques and humans immunized with germline-targeting (gt) BG505 GT1.1 SOSIP with adjuvant, and the opportunities provided by the infant RM model to define the specific biological factors that determine B cell lineage commitment by comparing vaccinees with or without bnAb development. Systems biology approaches can be useful to define early immune and molecular gene signatures after the vaccine prime immunization and the role of the intestinal microbiome in vaccine-induced bnAb development. Applying systems biology approaches, the objective of the overall studies is to determine how the modulation of the vaccine prime by different adjuvants and vaccine delivery platforms (Project 1) and changes in the infant microbiome (Project 2) alter the developmental pathways that lead to the induction of bnAbs. We hypothesize that the dynamic nature of the infant immune system and microbiome can be exploited to optimize the induction of bnAbs by HIV vaccines. These questions will be addressed via studies in the infant macaque model. The Nonhuman Primate (NHP) Core is an integral component of the overall HIVRAD Program and provides direct support to the Projects by coordinating and implementing all the NHP experiments (including regulatory approvals, and all procedures related to immunizations and sample collections). This Core has a longstanding track-record of collaboration with the 2 Project Leads/Overall P.I’s, and will communicate frequently with both Projects and other Cores to assure all the experimental needs are met with due diligence. The NHP Core uses the unique resources and infrastructure of the California National Primate Research Center (CNPRC), out of which it operates, and the expertise of the Core Lead and staff. The CNPRC is built on a service-oriented and interdisciplinary mission of advancing non-human primate models of human diseases and translational research. Resources at CNPRC include a large rhesus macaque breeding colony, experience with time-mated pregnancies and rearing of infant macaques, and all other procedures of monitoring and sample collections that are essential to the successful completion of the Projects.

抽象-非人灵长类核心(核心B) 只有当一种有效的疫苗方案能够实现长效... 长期保护性免疫，类似于几乎消除了其他全球病原体的疫苗。这个 诱导针对HIV包膜(Env)的广谱中和抗体(BNAbs)被认为对 有效的艾滋病毒疫苗。然而，尽管环境特异性抗体及其同源物的共同进化被描绘出来 从生殖系bcr到bNAbs的env中间体，很少有HIV疫苗策略能成功地诱导出 具有广泛的异源中和能力的HIV包膜抗体。我们对影响B的关键因素的认识 细胞分化和谱系承诺仍然有限。 建议的研究是建立在先前研究观察到的bNAbs在~ 50%-60%的婴儿和成年恒河猴和人类接种了生殖系靶向(GT)BG505 GT1.1 辅助剂，以及婴儿RM模型提供的机会，以定义特定的生物学 通过比较有或没有发育bNab的受试者来决定B细胞谱系承诺的因素。 系统生物学方法可用于定义早期免疫和分子基因特征。 疫苗初始免疫和肠道微生物群在疫苗诱导的bNab发育中的作用。 应用系统生物学的方法，整体研究的目标是确定如何调节 不同佐剂和疫苗投放平台的初级疫苗(项目1)和婴儿的变化 微生物组(项目2)改变导致bNAbs诱导的发育途径。我们假设 可以利用婴儿免疫系统和微生物组的动态性质来优化诱导 HIV疫苗对bNAbs的影响。这些问题将通过对婴儿猕猴模型的研究来解决。 非人灵长类(NHP)核心是整个HIVRAD计划的组成部分， 通过协调和实施所有NHP实验，为项目提供直接支持 (包括监管批准，以及与免疫接种和样本采集有关的所有程序)。这 CORE拥有与2个项目负责人/整体P.I合作的长期记录，并将 经常与项目和其他核心进行沟通，以确保满足所有实验需求 尽职调查。NHP核心使用加州国家灵长类动物独特的资源和基础设施 研究中心(中国石油天然气集团公司)，以及核心领导和工作人员的专业知识。中国人民大会党 是建立在面向服务和跨学科的使命之上的，即推动人类的非人类灵长类模型 疾病和翻译研究。CNPRC的资源包括一个大型恒河猴繁殖群体， 有时间配对怀孕和哺育猕猴幼崽的经验，以及所有其他程序 监测和样品采集对项目的成功完成至关重要。