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

在过去的一年中，病毒学实验室与其他内部NIAID实验室和其他外部合作者合作，开发了假病毒中和试验和表达融合前稳定的SARS-CoV-2刺突三聚体（mRNA-1273）的mRNA疫苗。对于中和试验，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规程。实验室工作人员正在使用该检测方法评估来自COVID-19康复者和Moderna mRNA 1273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，这是具有治疗和预防用途的巨大潜力的有价值的研究试剂。 对于mRNA疫苗，我们表明mRNA-1273诱导了对野生型（D 614）和D 614 G突变体2 SARS-CoV-2的有效中和抗体应答，以及高T细胞应答。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和鼻子免受SARS-CoV-2感染，而没有免疫病理学证据。用mRNA-1273接种的非人灵长类动物诱导了强烈的免疫应答，在上呼吸道和下呼吸道中具有快速保护，并且在肺中没有病理变化。参与临床试验的疫苗接种者对SARS-CoV-2表现出了强有力的中和反应。

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.