Immunogenicity and Efficacy of SARS-CoV-2 stabilized prefusion Spike protein vaccines in infant rhesus macaques

SARS-CoV-2 稳定预灌注 Spike 蛋白疫苗在幼年恒河猴中的免疫原性和功效

• 批准号: 10223634
• 负责人: Kristina De Paris
• 金额: $ 20.34万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-10 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223634
• 关键词: 2019-nCoV; Adolescence; Adult; Age; Antibodies; Antibody Response; Antigens; Award; B-Lymphocytes; Birth; Bypass; COVID-19; COVID-19 pandemic; Cell Lineage; Cessation of life; Childhood; Complement; Consumption; Coronavirus; Data; Development; Disease; Disease Outbreaks; Elderly; Exhibits; HIV; HIV vaccine; Hepatitis B; Human; Immune; Immune response; Immune system; Immunity; Immunoglobulin G; Immunology; Individual; Infant; Infection; Investigation; Life; Longevity; Lung; Lung diseases; Macaca; Macaca mulatta; Mediating; Memory; Messenger RNA; Middle East Respiratory Syndrome; Middle East Respiratory Syndrome Coronavirus; Modeling; Molecular; Mucous Membrane; Mus; Parents; Pathway interactions; Physiology; Plasma; Population; Positioning Attribute; Prevention; Proteins; Public Health; RNA vaccine; Risk; SARS coronavirus; Safety; Schedule; Severe Acute Respiratory Syndrome; Severities; System; Systems Biology; T cell response; Testing; Time; Vaccination; Vaccines; Viral; Virus; Virus Diseases; Virus Receptors; Work; age group; base; combat; comorbidity; coronavirus disease; experimental study; fighting; high risk population; human data; immunogenicity; infancy; lipid nanoparticle; neonatal infection; neutralizing antibody; nonhuman primate; novel coronavirus; novel vaccines; pandemic disease; parent grant; pre-clinical; preclinical safety; predictive signature; prevent; response; safety testing; vaccine candidate; vaccine development; vaccine efficacy; vaccine response; vaccine trial

ABSTRACT The emergence of the highly-transmissible novel coronavirus SARS-CoV-2 has led to a global pandemic of severe respiratory disease. While elderly individuals and adults with co-morbidities are high risk populations, coronavirus disease (COVID-19) can occur in individuals across all age groups, including infants. Therefore, it will be important to develop a vaccine that can be administered in early life and generate long term immunity to end the COVID19 pandemic. While initial safety testing of vaccine candidates will occur in adult populations, there are many potential advantages of targeting the vaccine to the pediatric vaccine schedule including high rates of pediatric vaccine coverage and potential for lifelong immunity. In fact, infants can respond remarkably well to protein antigens, including the hepatitis B and candidate HIV envelope vaccines, and there is evidence that HIV-infected infants are better equipped to generate HIV-neutralizing antibodies. Moreover, our previous work in human and rhesus monkeys has established that infants are able to generate HIV Env vaccine responses of comparable or higher magnitude to that of adults that persist for months and are able to be boosted. The parent grant P01 AI117915-06 “Early Life Vaccination to Prevent HIV Acquisition in Adolescence” aims to assess candidate HIV envelope mRNA and SOSIP trimer vaccines in infant rhesus monkey nonhuman primate model and determine their efficacy against HIV acquisition in adolescence. As related complementary studies, we propose to assess the immunogenicity and efficacy of candidate SARS-CoV-2 spike (S) protein and mRNA vaccine candidates in infant rhesus monkeys. We hypothesize that infants can mount effective and persistent systemic and mucosal antibody responses to SARS-CoV-2 vaccination that will protect against virus challenge. This work will provide preclinical safety, immunogenicity, and efficacy data on leading SARS-CoV-2 vaccine platforms that can de-risk human trials in pediatric populations and justify bypassing time consuming and expensive age de-escalation studies. The end of the SARS-CoV-2 pandemic will require high global coverage with a vaccine that prevents viral spread and generates long lasting immunity, which may best be achieved with a pediatric targeted vaccine.

抽象的 高传染性新型冠状病毒 SARS-CoV-2 的出现导致全球大流行 患有严重呼吸道疾病的老年人和患有合并症的成年人是高危人群， 冠状病毒病（COVID-19）可发生在所有年龄段的个体中，包括婴儿。 开发一种可以在生命早期接种并产生长期免疫力的疫苗非常重要 虽然候选疫苗的初步安全测试将在成年人中进行， 将疫苗纳入儿科疫苗计划有许多潜在的优势，包括高 儿科疫苗覆盖率和终身免疫的潜力 事实上，婴儿的反应可能会异常。 蛋白质抗原，包括乙型肝炎包膜和候选艾滋病毒疫苗，并且有证据表明 感染艾滋病毒的婴儿更有能力产生艾滋病毒中和抗体。 对人类和恒河猴的研究表明，婴儿能够产生 HIV Env 疫苗 与成年人相当或更高程度的反应，持续数月，并且能够 家长补助金 P01 AI117915-06“早期疫苗接种以预防青春期感染艾滋病毒”。 旨在评估非人类幼年恒河猴的候选 HIV 包膜 mRNA 和 SOSIP 三聚体疫苗 灵长类动物模型并确定其对青春期艾滋病毒感染的功效作为相关补充。 研究中，我们建议评估候选 SARS-CoV-2 刺突 (S) 蛋白的免疫原性和功效， 我们致力于让婴儿恒河猴能够有效地接种 mRNA 疫苗。 对 SARS-CoV-2 疫苗接种产生持续的全身和粘膜抗体反应，这将保护 这项工作将提供有关抗病毒挑战的临床前安全性、免疫原性和功效数据。 领先的 SARS-CoV-2 疫苗平台可以降低儿科人群人体试验的风险并证明其合理性 绕过耗时且昂贵的年龄降级研究 SARS-CoV-2 大流行的结束。 将需要疫苗在全球范围内实现高覆盖率，以防止病毒传播并产生持久的免疫力， 这最好通过儿科靶向疫苗来实现。