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.

摘要-非人灵长类核心（核心B） 只有当有效的疫苗方案能够长期有效地预防艾滋病毒/艾滋病， 保护性免疫，类似于几乎消灭了全球其他病原体的疫苗。的 针对HIV包膜（Env）的广泛中和抗体（bnAb）的诱导被认为对于HIV感染的预防至关重要。 有效的艾滋病疫苗。然而，尽管描绘了Env特异性抗体及其同源物的共同进化， Env是从生殖系BCR到bnAb的中间体，很少有HIV疫苗策略成功地诱导了 具有广泛的异源中和能力的HIV Env Ab。我们对影响B的关键因素的了解 细胞分化和谱系定型仍然有限。 所提出的研究是建立在对~ 2000年bnAb发展的先前研究观察的基础上的。 50-60%的婴儿和成年恒河猴和人接种了生殖系靶向（gt）BG 505 GT 1.1 SOSIP与佐剂，以及婴儿RM模型提供的机会，以确定特定的生物学特性， 通过比较有或没有bnAb发展的疫苗接种者来确定B细胞谱系定型的因素。 系统生物学方法可用于在免疫后定义早期免疫和分子基因特征。 疫苗初免和肠道微生物组在疫苗诱导的bnAb发展中的作用。 应用系统生物学方法，整体研究的目标是确定如何调节 通过不同佐剂和疫苗输送平台（项目1）进行的疫苗初免以及 微生物组（项目2）改变导致bnAb诱导的发育途径。我们假设 婴儿免疫系统和微生物组的动态性质可以用来优化诱导 bnAbs通过HIV疫苗。这些问题将通过在幼年猕猴模型中的研究来解决。 非人灵长类（NHP）核心是整个HIVRAD计划的一个组成部分， 通过协调和实施所有NHP实验，为项目提供直接支持 （包括监管部门的批准，以及与免疫接种和样本采集相关的所有程序）。这 核心部门与2个项目负责人/总体P.I有长期的合作记录，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 Core使用加州国家灵长类动物中心的独特资源和基础设施 研究中心（CNPRC），它的运作，以及核心领导和工作人员的专业知识。CNPRC 是建立在一个面向服务和跨学科的使命，推进人类的非人类灵长类动物模型， 疾病和转化研究。CNPRC的资源包括一个大型恒河猴繁殖群， 时间交配怀孕和养育婴儿猕猴的经验，以及所有其他程序， 监测和样品收集对项目的成功完成至关重要。