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Principal Investigator: Wing Pui Kong
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $1,368,169
Funding agency: National Institute of Allergy and Infectious Diseases
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 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. Previously, we have shown that HBsAg nanoparticles displaying six-proline-stabilized spike S6P (S6P-HBsAg) of SARS-CoV-2 elicits more potent and more durable neutralizing antibody (nAb) responses than stabilized spikes via genetic delivery.
Here, we investigated whether genetic delivery with sarbecovirus S6P-HBsAg nanoparticles could achieve more potent and broader neutralizing antibody (nAb) responses than that of stabilized spikes. In both aged and young mice, one heterologous genetic delivery following two homologous genetic deliveries with sarbecovirus stabilized spike or S6P-HBsAg nanoparticles elicited low levels of cross nAb responses. While two heterologous genetic deliveries with sarbecovirus full-length S2P failed to elicit potent cross nAb responses against sarbecoviruses, two heterologous genetic deliveries with S6P-HBsAg elicited highly potent nAb responses against both SARS-CoV-1 and SARS-CoV-2 pseudoviruses. Conversely, in young mice, homologous genetic deliveries with only sarbecovirus full-length S2P but not S6P-HBsAg elicited cross nAb responses, but at low levels. Co-immunizations with SARS-CoV-1 and SARS-CoV-2 S6P-HBsAg DNAs elicited potent cross nAb responses against both sarbecoviruses.
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