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. For the past last year, we are testing various new designs of non-infectious self-assembly Virus-Like-Particle (VLP) expressing the SARS-CoV-2 spike on the nanoparticles' surface as a potential improved vaccine which may elicit stronger and prolong immune responses. We are testing two concepts, first one is to see if we can express and produce VLPs with target antigens on the VLP surface, the second one is to use gene-base vaccine approach for delivering the modified VLP gene directly in order to avoid the common problems involving the production of the modified VLPs immunogens. We first assessed whether hepatitis B surface antigen (HBsAg)-based nanoparticles and also lumazine synthase nanoparticles with SARS-CoV-2 spike can elicit potent and long lasting immunity against SARS-CoV-2 in mice . The data showed that genetic delivery of SARS-CoV-2 S6P-HBsAg and also on lumazine synthase nanoparticles can both elicit potent and durable neutralizing antibody (nAb) responses. S6P-HBsAgs can elicit substantially more potent nAb responses than S2P matching mRNA-1273 in mice. Our findings highlight the potential of S6P-HBsAgs as next generation genetic vaccine candidates against SARS-CoV-2. Furthermore, we are testing antigen protein mucosal boosting after the initial gene-based prime immunization would elicit improved immune responses or not.