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

在过去的几年里，病毒学实验室与其他NIAID内部实验室和其他外部合作者合作，开发了一种假病毒中和试验和一种表达融合稳定的SARS-CoV-2尖峰三聚体(mRNA-1273)的mRNA疫苗。对于中和试验，我们已经为其他VRC实验室提供了技术和软件帮助，并制定了共同的标准操作程序。随着世界上不断出现更多的SARS-CoV-2变异病毒，我们不断地制造与新出现的变异病毒相对应的各种伪病毒。更重要的是，假病毒中和试验也需要进行修改，以适应新的变异病毒，以便该试验的适当使用。实验室工作人员正在使用这种分析方法来评估来自新冠肺炎恢复者和现代mRNA1273疫苗临床试验志愿者的人类血清样本。我们还在从新冠肺炎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，具有巨大的潜力，可用于治疗和预防不断出现的SARS-CoV-2变异株。 对于信使核糖核酸疫苗，我们发现，信使核糖核酸-1273能诱导对SARS-CoV-2初始毒株和变异株的中和抗体反应，以及高T细胞反应。重要的是，临床试验中的这种mRNA疫苗对SARS-CoV-2表现出了强大的中和反应。我们正在测试各种新的非传染性自组装类病毒颗粒(VLP)，这种颗粒在颗粒表面表达SARS-CoV-2尖峰，作为一种潜在的疫苗，可能会产生更好的抗体。由于信使核糖核酸疫苗已被证明是一个非常成功的疫苗平台，我们将继续在基因(信使或DNA)平台上开发VLP疫苗候选平台。

During the past years, 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. Since more SARS-CoV-2 variant viruses continuously arise in the world, we are continuously making various pseudoviruses corresponding to the emerging variant viruses. And more importantly, the pseudovirus neutralization assay also needed to be modified to adapted to the new variant viruses for the assay appropriate usage. The assay is being used by laboratory staff to evaluate human serum samples from individuals recovering from COVID-19 and from volunteers in the 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 against the continuously emerging SARS-CoV-2 variants. For the mRNA vaccine, we show that mRNA-1273 induces potent neutralizing antibody responses to the initial strain and variant SARS-CoV-2, as well as high T cells responses. Importantly, this mRNA vaccine in the clinical trial have shown a robust neutralizing response to SARS-CoV-2. We are testing various new designs of non-infectious self-assembly Virus-Like-Particle (VLP) expressing the SARS-CoV-2 spike on the particles' surface as a potential vaccine which may elicit better antibodies. Since the mRNA vaccine has proved to be a highly successful vaccine platform, we will continue to develop the VLP vaccine candidates in genetic (mRNA or DNA) platform.