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

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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.