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

由于COVID-19没有有效的治疗方法。尽管mRNA疫苗被授权用于紧急使用，但这两种mRNA疫苗提供的保护的持久性仍然令人担忧，因为在COVID患者的恢复期血清中，刺突特异性抗体迅速下降。在过去几年中，病毒学实验室与NIAID的其他内部实验室和其他外部合作者合作，开发了一种更有效和持久的疫苗，用于控制正在进行的大流行和预防未来的爆发。 虽然已有数种COVID-19疫苗投入使用，但仍需要更有效及持久的疫苗以对抗持续的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 spike-HBsAg纳米颗粒，在HBsAg核心上显示六脯氨酸稳定的WA 1（野生型，WT）spike S6 P。这些S6 P-SARSAg结合不同结构域特异性SARS-CoV-2单克隆抗体。在有和没有HBV预接种的小鼠中，与可溶性S2 P或S6 P或其编码序列匹配mRNA-1273的全长S2 P相比，用S6 P-Ags进行DNA免疫可引起针对不同SARS-CoV-2毒株的更有效和持久的中和抗体（nAb）应答。由S6 P-SAAg引起的nAb应答比可溶性S2 P或S6 P持续时间长得多，并且似乎被HBsAg预暴露增强。这些数据表明，SARS-CoV-2 S6 P-HBsAg纳米颗粒的遗传递送可以比非纳米颗粒形式的稳定化刺突引起更大和更持久的nAb应答。我们的研究结果强调了S6 P-SARS-CoV-2作为下一代基因疫苗候选物的潜力。 与此同时，我们正在测试我们是否可以表达和生产具有靶向COVID-19抗原或VLP表面上的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应答。

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.