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: 10928628
• 负责人: Wing Pui Kong
• 金额: $ 28.54万
• 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/10928628
• 关键词: 2019-nCoV; Antibodies; Antibody Response; Binding; COVID-19; COVID-19 pandemic; COVID-19 patient; COVID-19 vaccine; Code; Collaborations; Coronavirus; DNA; Data; Development; Epitopes; FDA Emergency Use Authorization; Genetic; Hepatitis B Surface Antigens; Hepatitis B Virus; Human; Immune response; Immunization; Laboratories; Length; Moderna COVID-19 vaccine; Monoclonal Antibodies; Mus; National Institute of Allergy and Infectious Disease; Proline; RNA vaccine; Reporting; SARS-CoV-2 antigen; SARS-CoV-2 infection; Surface; Testing; Vaccination; Vaccinee; Vaccines; Viral; combat; future outbreak; genetic vaccine; immunogenic; nanoparticle; neutralizing antibody; next generation; pandemic disease; pre-clinical; prevent; self assembly; vaccine candidate; virology

Since there is no effective cure for COVID-19. Though the mRNA vaccines were authorized for emergency use, the durability of protection provided by these two mRNA vaccines is still a concern, given the fact that the spike-specific antibodies decline rapidly in convalescent sera of COVID patients. During the past years, the Virology Laboratory has collaborated with other intramural NIAID labs and other external collaborators to develop a more effective and long-lasting vaccine for controlling the ongoing pandemic and for preventing future outbreaks. While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBsAg nanoparticles displaying a six-proline-stabilized WA1 (wild type, WT) spike S6P on a HBsAg core. These S6P-HBsAgs bound diverse domain-specific SARS-CoV-2 monoclonal antibodies. In mice with and without a HBV pre-vaccination, DNA immunization with S6P-HBsAgs elicited significantly more potent and durable neutralizing antibody (nAb) responses against diverse SARS-CoV-2 strains than that of soluble S2P or S6P, or full-length S2P with its coding sequence matching mRNA-1273. The nAb responses elicited by S6P-HBsAgs persisted substantially longer than by soluble S2P or S6P and appeared to be enhanced by HBsAg pre-exposure. These data show that genetic delivery of SARS-CoV-2 S6P-HBsAg nanoparticles can elicit greater and more durable nAb responses than non-nanoparticle forms of stabilized spike. Our findings highlight the potential of S6P-HBsAgs as next generation genetic vaccine candidates against SARS-CoV-2. Meanwhile, we are testing to see if we can express and produce various VLPs with target COVID-19 antigens or other viral conserved epitopes on the VLP surface to elicit more potent immune responses against COVID-19 and also other coronaviruses.

由于 COVID-19 没有有效的治疗方法。尽管 mRNA 疫苗被授权紧急使用，但这两种 mRNA 疫苗提供的保护的持久性仍然令人担忧，因为新冠病毒患者恢复期血清中的刺突特异性抗体迅速下降。在过去的几年中，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，开发一种更有效、更持久的疫苗，以控制当前的大流行并预防未来的疫情爆发。 虽然多种 COVID-19 疫苗已投入使用，但仍需要更有效、更持久的疫苗来对抗持续的 COVID-19 大流行。在这里，我们报告了高度免疫原性的自组装 SARS-CoV-2 刺突 HBsAg 纳米颗粒，在 HBsAg 核心上展示了六脯氨酸稳定的 WA1（野生型，WT）刺突 S6P。这些 S6P-HBsAg 结合不同的域特异性 SARS-CoV-2 单克隆抗体。在预先接种或未接种 HBV 疫苗的小鼠中，与可溶性 S2P 或 S6P 或编码序列与 mRNA-1273 匹配的全长 S2P 相比，使用 S6P-HBsAg 进行 DNA 免疫可引发针对不同 SARS-CoV-2 毒株的更有效、更持久的中和抗体 (nAb) 反应。 S6P-HBsAg 引发的 nAb 反应持续时间明显长于可溶性 S2P 或 S6P，并且 HBsAg 预暴露似乎增强了这种反应。这些数据表明，与非纳米颗粒形式的稳定刺突相比，SARS-CoV-2 S6P-HBsAg 纳米颗粒的基因传递可以引发更强、更持久的 nAb 反应。我们的研究结果强调了 S6P-HBsAg 作为下一代 SARS-CoV-2 基因疫苗候选者的潜力。 与此同时，我们正在测试是否可以表达和生产具有目标 COVID-19 抗原或 VLP 表面其他病毒保守表位的各种 VLP，以引发针对 COVID-19 和其他冠状病毒的更有效的免疫反应。