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 - 非人类灵长类动物核心（核心B） 艾滋病毒/艾滋病流行的终结只有在有效的疫苗方案可以长期实现时才成功 术语受保护的免疫力，类似于几乎消除其他全球病原体的疫苗。 诱导对HIV包膜（ENV）的广泛中和抗体（BNAB）被认为至关重要 有效的HIV疫苗。然而，尽管描绘了ENV特异性抗体的共同进化及其同源 ENV中间体从种系BCR到BNAB，很少有HIV疫苗策略成功地引起 HIV Env ABS具有广泛的异源神经化能力。我们对关键因素影响b的知识 细胞分化和谱系承诺仍然有限。 拟议的研究建立在先前有关bnabs发展的研究基础的基础上。 50-60％的婴儿和成年恒河猕猴和人类用种系靶向（GT）BG505 GT1.1免疫 调整的SOSIP以及婴儿RM模型提供的定义特定生物学的机会 通过比较有或没有BNAB发育的疫苗来决定B细胞谱系承诺的因素。 系统生物学方法对于定义早期免疫和分子基因特征是有用的 疫苗素免疫和肠道微生物组在疫苗诱导的BNAB发育中的作用。 应用系统生物学方法，总体研究的目的是确定调制如何 不同的调节器和疫苗输送平台（项目1）的疫苗素数和婴儿的变化 微生物组（项目2）改变了导致BNAB诱导的发育途径。我们假设 可以探索婴儿免疫系统和微生物组的动态性质以优化诱导 HIV疫苗的BNAB。这些问题将通过婴儿猕猴模型中的研究解决。 非人类灵长类动物（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 （包括法规批准以及与免疫和样品收集有关的所有程序）。这 Core与2个项目主角/总体P.I的合作录制了很长的曲目，并将 经常与两个项目和其他核心进行沟通，以假设满足所有实验需求 尽职调查。 NHP核心使用加利福尼亚国家灵长类动物的独特资源和基础设施 研究中心（CNPRC），其运营以及核心负责人和员工的专业知识。 CNPRC 建立在以服务为导向和跨学科的使命中，以推进人类的非人类灵长类动物模型 疾病和翻译研究。 CNPRC的资源包括一个大的恒河猕猴繁殖殖民地， 具有时间融合怀孕的经验和婴儿猕猴的饲养以及所有其他程序 对项目成功完成至关重要的监视和样品收集。