Nonhuman Primate Core (NHP Core/Core 1)

非人类灵长类核心（NHP 核心/核心 1）

基本信息

批准号：
10602515
负责人：
Sallie R. Permar
金额：
$ 48.02万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10602515
关键词：
4 year old AIDS prevention Achievement Adherence Adolescence Adolescent Adult Animal Model Animals Antibodies Antibody Response B-Lymphocytes Biological Assay Breast Feeding Breeding California Cell Lineage Childhood Clinical Clinical Data Clinical Research Collaborations Communication Data Databases Decision Making Dedications Development Dose Electronic Mail Ensure Epidemic Goals HIV HIV Infections HIV vaccine HIV-1 HIV-infected adolescents HIV/AIDS Health Housing Immune response Immune system Immunity Immunization Immunologics Immunology Infant Infection Infrastructure Lead Life Macaca Macaca mulatta Maintenance Measures Messenger RNA Mission Modeling Monitor North Carolina Paris, France Partner in relationship Pathogenesis Physiology Plasma Preclinical Testing Pregnancy Prevention Primates Procedures Progress Reports RNA vaccination Rectum Regimen Research Research Project Grants Resources Risk Route SIV Safety Sampling Services Sexual Transmission Specificity System Testing Time Translational Research Universities Update Vaccination Vaccine Research Vaccines Viral Virus age effect age related animal data design experience experimental study human disease human model in utero infancy meetings microbiome neutralizing antibody nonhuman primate pathogen preadolescence preclinical study prevent programs rectal response sample collection sexual debut simian human immunodeficiency virus symposium transmission process vaccine development vaccine efficacy vaccine evaluation vaccine platform vaccine strategy viral RNA

项目摘要

ABSTRACT – Nonhuman Primate Core (NHP Core/ Core 1) 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. HIV acquisition risk begins in utero and continues through the period of breastfeeding, then starts again at the time of sexual debut and continues into adulthood. Prevention of HIV through adulthood will require an active vaccine that elicits persistent immunity. Yet, current HIV vaccine platforms have failed to induce highly- protective immunity in adults in preclinical and clinical studies. Excitingly, recent studies indicate that achieving durable, polyfunctional, and bnAb responses following HIV infection may be more easily achieved in infancy than in an adult immune system. Yet, gaps remain in our understanding of whether HIV vaccination in early life is advantageous for achievement of protective, long lasting HIV immunity. Because of its many similarities in development, physiology, immunology and pathogenesis, nonhuman primate (NHP) models of HIV infection are highly appropriate to explore these research questions. Thus, this HIVRAD Program will use the NHP model to test the hypothesis that HIV Env vaccine platforms administered in early life and boosted in pre- adolescence will achieve durable, polyfunctional, and mature immune responses that will be more efficacious at prevention of sexual transmission than immunization starting in preadolescence. In this renewal, the NHP Core will continue to support NHP studies in Project 1, “Age-related impact on early life B cell lineage-designed SOSIP HIV Env vaccination” (P.I. Dr. S. Permar, Duke University) and Project 2, “RNA vaccination in early life to induce potent and broad HIV Env-specific antibody responses“ (P.I. Dr. K. De Paris, UNC-CH). Projects test the same hypothesis using 2 different vaccine platforms, SOSIP and mRNA-LNP, respectively. The Nonhuman Primate Core (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), and by developing/testing a repeated low-dose rectal SHIV challenge model in adolescent macaques to test vaccine efficacy. 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, nursery-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（NHP核心/核心1）艾滋病毒/艾滋病流行的终结只有在有效的疫苗方案才能实现时才能成功长期保护的免疫力类似于几乎消除其他全球病原体的疫苗。艾滋病毒获取风险从子宫开始，一直持续到母乳喂养期，然后在性行会的时间并持续到成年。通过成年预防艾滋病毒将需要活跃引起持续免疫力的疫苗。然而，当前的HIV疫苗平台未能高度诱导临床前和临床研究成人的保护性免疫学。令人兴奋的是，最近的研究表明实现艾滋病毒感染后耐用，多功能和BNAB反应可能更容易在婴儿期实现比在成人免疫系统中。然而，差距仍然在我们对早期艾滋病毒疫苗接种中是否的理解中仍然存在有利于实现受保护的，持久的艾滋病毒免疫力。因为它的许多相似之处 HIV感染的发展，生理，免疫学和发病机理，非人类灵长类动物（NHP）模型非常适合探索这些研究问题。那是Hivrad程序将使用NHP 测试假设的模型，即在早期生命中给药并在预先提高的假设青少年将获得持久，多功能和成熟的免疫反应，这将更有效预防性传播时，比从辉煌开始的免疫传播。在此续约中，NHP 核心将继续支持项目1中的NHP研究，“与年龄相关的对早期生命B细胞谱系设计的影响 SOSIP HIV ENV疫苗接种”（P.I. S. Permar博士，杜克大学）和项目2，“早期RNA疫苗接种引起潜在和广泛的HIV特异性抗体反应”（P.I. K. de Paris博士，UNC-CH）。项目测试使用2个不同的疫苗平台SOSIP和mRNA-LNP的相同假设。非人类灵长类动物核心（NHP Core）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，以及与免疫和样本收集有关的所有程序）以及在青少年猕猴中开发/测试重复的低剂量直肠SHIV挑战模型以测试疫苗功效。该核心与2个项目主角/总体P.I和将经常与两个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核心使用加利福尼亚国家的独特资源和基础设施它运营的灵长类动物研究中心（CNPRC）以及核心负责人和员工的专业知识。这 CNPRC建立在面向服务和跨学科的使命之上，以推动非人类灵长类动物模型人类疾病和翻译研究。 CNPRC的资源包括大恒河猕猴育种殖民地，有及时妊娠的经验，婴儿猕猴的育苗和所有程序对项目成功完成至关重要的监视和样品收集。