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: 10497761
• 负责人: John Mascola
• 金额: $ 39.31万
• 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/10497761
• 关键词: 2019-nCoV; Animals; Antibodies; Antibody Response; Biological Assay; COVID-19; Clinical; Clinical Trials; Computer software; DNA; Development; Disease; Enzyme-Linked Immunosorbent Assay; Genetic; Human; Immunize; Individual; Laboratories; Messenger RNA; Moderna COVID-19 vaccine; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Prevention; Procedures; RNA vaccine; Reagent; Research; SARS-CoV-2 infection; SARS-CoV-2 variant; Sampling; Serum; Standardization; Surface; T cell response; Testing; Therapeutic; Vaccinated; Vaccines; Variant; Virus; Virus-like particle; design; neutralizing antibody; particle; pre-clinical; response; self assembly; vaccine candidate; vaccine evaluation; vaccine-induced antibodies; virology; volunteer

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.

在过去的几年中，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。由于世界上不断出现更多的SARS-CoV-2变异病毒，我们也在不断地制作与新出现的变异病毒相对应的各种假病毒。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，以便试验适当使用。 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变体。 对于mRNA疫苗，我们表明mRNA-1273诱导对初始菌株和变体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疫苗在临床试验中显示出对SARS-CoV-2的强大中和反应。 我们正在测试各种新设计的非感染性自组装病毒样颗粒（VLP），在颗粒表面表达SARS-CoV-2刺突，作为可能引发更好抗体的潜在疫苗。由于mRNA疫苗已被证明是一个非常成功的疫苗平台，我们将继续在遗传（mRNA或DNA）平台上开发VLP疫苗候选物。