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.

项目摘要-核心D：非人灵长类 新冠肺炎已经为病原体迅速传播到所有范围的能力敲响了警钟。 并建立一种持久的大流行，带来相当大的疾病、死亡和经济损失。而当 在非典和中东呼吸综合征之前，新冠肺炎的传染性明显增强，而且从所有实际目的来看 不受现有抗病毒疗法的影响，导致广泛传播，并导致 具有较高传播适合度的免疫截然不同的突变体。而且，新冠肺炎是第三种冠状病毒 21世纪一直威胁着人类、野生动物和各种蝙蝠的人畜共患病 特别是已被证明携带其他几种冠状病毒，容易传播和 产生更多的流行病/大流行。该计划的总体目标是设计和开发 泛肉瘤病毒和泛贝塔冠状病毒疫苗都可以先发制人地防止这种广泛传播 人畜共患传播，使用基于结构的免疫原设计方法。 核心D(非人灵长类，维林格)的目标将是初步评估最有希望的免疫原 在啮齿动物中进行筛选，结合临床相关佐剂诱导保护性体液和细胞 食蟹猴的免疫反应，作为与人类关系更密切的模型。核心将是 负责进行非人类灵长类动物实验，来自动物采购，动物 描述、满足法规要求、规划和实施灵长类免疫以及 样品的采集、加工、储存和分发给该计划的合作伙伴。结果： 这些研究有望反复提炼和优化免疫原/佐剂配方，并提供 导致PAN肉瘤病毒和PAN贝塔冠状病毒疫苗验证的数据将被翻译成 诊所。