Pre-clinical Vaccine and Antibody Development for Coronavirus Disease 2019 (COVID-19)

2019 年冠状病毒病 (COVID-19) 的临床前疫苗和抗体开发

• 批准号: 10274162
• 负责人: John Mascola
• 金额: $ 25.35万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10274162
• 关键词: 2019-nCoV; Animals; Antibodies; Antibody Response; Biological Assay; COVID-19; Clinical; Clinical Trials; Computer software; Development; Disease; Enzyme-Linked Immunosorbent Assay; Human; Immune response; Immunize; Individual; Infection; Laboratories; Lung; Messenger RNA; Monoclonal Antibodies; Mus; National Institute of Allergy and Infectious Disease; Nose; Pathologic; Phase I Clinical Trials; Prevention; Procedures; RNA vaccine; Reagent; Research; Sampling; Serum; Standardization; T cell response; Therapeutic; Vaccinated; Vaccines; Virus; immunopathology; neutralizing antibody; nonhuman primate; pre-clinical; response; vaccine candidate; virology; volunteer

During the past year, the Virology Laboratory has collaborated with other intramural NIAID labs and other external collaborators to develop a pseudovirus neutralization assay and an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). For the neutralization assay, we have provided technical and software assistance to other VRC labs, and developed a shared Standard Operating Procedure. The assay is being used by laboratory staff to evaluate human serum samples from individuals recovering from COVID-19 and from volunteers in the Phase I clinical trial of the Moderna mRNA1273 vaccine. We are also isolating and characterizing monoclonal antibodies from individuals recovering from COVID-19 disease, assessing for SARS-CoV-2 neutralizing antibodies, which are valuable research reagents with great potential for therapeutic and prevention purposes. For the mRNA vaccine, we show that mRNA-1273 induces both potent neutralizing antibody responses to wild-type (D614) and D614G mutant2 SARS-CoV-2, as well as high T cells responses. Importantly, this mRNA vaccine protects against SARS-CoV-2 infection in the lungs and noses of mice and nonhuman primate without evidence of immunopathology. Vaccinated nonhuman primates with mRNA-1273 induced robust immune responses with rapid protection in the upper and lower airways, and no pathologic changes in the lung. Vaccine recipients participating in the clinical trial have shown a robust neutralizing response to SARS-CoV-2.

在过去的一年中，病毒学实验室与 NIAID 的其他校内实验室和其他外部合作者合作，开发了一种假病毒中和测定方法和一种表达预灌注稳定的 SARS-CoV-2 刺突三聚体 (mRNA-1273) 的 mRNA 疫苗。对于中和测定，我们为其他 VRC 实验室提供了技术和软件帮助，并制定了共享的标准操作程序。实验室工作人员正在使用该检测方法来评估从 COVID-19 中恢复的个体以及 Moderna mRNA1273 疫苗 I 期临床试验志愿者的人血清样本。我们还从 COVID-19 疾病康复者中分离和鉴定单克隆抗体，评估 SARS-CoV-2 中和抗体，这些抗体是有价值的研究试剂，在治疗和预防方面具有巨大潜力。 对于 mRNA 疫苗，我们发现 mRNA-1273 可诱导针对野生型 (D614) 和 D614G 突变体 2 SARS-CoV-2 的有效中和抗体反应，以及高 T 细胞反应。重要的是，这种 mRNA 疫苗可以保护小鼠和非人灵长类动物的肺部和鼻子免受 SARS-CoV-2 感染，而无需免疫病理学证据。接种 mRNA-1273 疫苗的非人灵长类动物诱导了强烈的免疫反应，对上呼吸道和下呼吸道产生快速保护，并且肺部没有病理变化。参与临床试验的疫苗接种者表现出对 SARS-CoV-2 的强烈中和反应。