Core D: Nonhuman Primates

核心 D：非人类灵长类动物

• 批准号: 10425029
• 负责人: Francois J Villinger
• 金额: $ 152.77万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-02 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10425029
• 关键词: 2019-nCoV; Abate; Adjuvant; Animal Model; Animals; Antibodies; Antigens; Antiviral Therapy; B-Lymphocytes; Brazil; COVID-19; COVID-19 pandemic; COVID-19 vaccine; Cells; Cessation of life; Chiroptera; Clinic; Collaborations; Coronavirus; Coronavirus Infections; Data; Development; Disease; Distant; Economics; Epidemic; Epitopes; Evaluation; Event; Evolution; Experimental Designs; Formulation; Funding; Future; Generations; Genome; Goals; Herd Immunity; Human; Immune; Immune response; Immunization; Immunologics; India; Lead; Macaca fascicularis; Middle East Respiratory Syndrome; Modeling; Mosaicism; Patients; Performance; Persons; Phase; Phase II Clinical Trials; Plasma Cells; Plasmablast; Population; Primates; Process; Rodent; SARS-CoV-2 B.1.351; Sampling; Sarbecovirus; Scaffolding Protein; Secure; Severe Acute Respiratory Syndrome; South African; South American; Specificity; Structure; Surface; T-Lymphocyte; Testing; Time; Translating; Vaccinated; Vaccination; Vaccine Design; Vaccines; Validation; Variant; Viral; Virulence; Virus; Work; Zoonoses; base; betacoronavirus vaccine; clinically relevant; coronavirus vaccine; design; economic cost; experimental study; fitness; flexibility; improved; mortality; mutant; nanoparticle; neutralizing antibody; nonhuman primate; novel; novel coronavirus; pandemic disease; pathogen; post SARS-CoV-2 infection; prevent; programs; protective efficacy; receptor binding; response; sample collection; transmission process; vaccine candidate; vaccine efficacy; vaccine trial; virology; ward; zoonotic coronavirus

PROJECT SUMMARY – CORE D: NONHUMAN PRIMATES COVID-19 has served as a wake-up call regarding the ability of a pathogen to rapidly spread to all confines of the world and establish a lasting pandemic, with considerable disease, death, and economic losses. While preceded by SARS and MERS, COVID-19 turned out markedly more contagious, and for all practical purposes impervious to existing antiviral therapies, leading to extensive spreading as well as giving rise to immunologically distinct mutants with higher transmission fitness. Moreover, COVID-19 is the third coronavirus zoonosis in the 21s century that has been threatening humans, and wildlife and various species of bats in particular have been demonstrated to harbor several other coronaviruses susceptible to transmitting and generating additional epidemics/pandemics. The overarching goal of this program is to design and develop both pan-sarbecovirus and pan-betacoronavirus vaccines to preemptively ward off such widely disseminated zoonotic transmission, using a structure-based immunogen design approach. The goal of Core D (Nonhuman Primates, Villinger) will be to evaluate the most promising immunogens initially screened in rodents, combined with clinically relevant adjuvants to elicit protective humoral and cellular immune responses in cynomolgus macaques, as a model more closely related to humans. The Core will be responsible for conducting the nonhuman primate experiments, from animal procurement, animal characterization, satisfying regulatory requirements, planning and execution of the primate immunizations and sample collections, processing, storage and distributions to collaborating partners of the Program. Results of these studies are expected to iteratively refine and optimize immunogen/adjuvant formulations and provide data leading to the validation of a pan sarbecovirus and a pan betacoronavirus vaccine to be translated to the clinic.

项目概要-核心D：非人灵长类动物 2019冠状病毒病敲响了警钟，提醒人们病原体有能力迅速传播到世界各地， 世界并建立一个持久的流行病，相当大的疾病，死亡和经济损失。而 在SARS和MERS之前，COVID-19的传染性明显更强， 不受现有抗病毒疗法的影响，导致广泛传播，并引起 具有更高传播适应性的免疫学上不同的突变体。此外，COVID-19是第三种冠状病毒 人畜共患病在21世纪世纪一直威胁着人类，野生动物和各种蝙蝠， 特别是已被证明携带其他几种冠状病毒， 产生额外的流行病/大流行病。该计划的总体目标是设计和开发 泛Sarbecovirus和泛β冠状病毒疫苗，以先发制人地抵御这种广泛传播的 人畜共患病传播，使用基于结构的免疫原设计方法。 核心D（非人灵长类动物，Villinger）的目标是最初评估最有希望的免疫原。 在啮齿类动物中筛选，与临床相关佐剂联合， 食蟹猴的免疫应答，作为与人类更密切相关的模型。芯会 负责进行非人类灵长类动物实验，从动物采购，动物 表征，满足监管要求，计划和执行灵长类动物免疫接种， 样品收集、处理、储存和分发给该计划的合作伙伴。结果 这些研究有望反复改进和优化免疫原/佐剂制剂 导致泛肉瘤病毒和泛β冠状病毒疫苗验证的数据将转化为 诊所