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Jonah S Merriam, Catherine Liu, Lingshu Wang, Wei Shi, Eun-Sung Yang, Yi Zhang, Wing-Pui Kong, Yaroslav Tsybovski, Tyler Stephens, Raffaello Verardi, Kwanyee Leung, Cody Stein, Man Chen, Adam Olia, Darcy Harris, Amarendra Pegu, Barney Graham, Peter Kwong, John Mascola, Richard Koup, Genetic immunization with self-assembling SARS-CoV-2 Spike-HBsAg nanoparticles, The Journal of Immunology, Volume 210, Issue Supplement_1, May 2023, Page 223.02, https://doi.org/10.4049/jimmunol.210.Supp.223.02
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Abstract
As the COVID-19 pandemic continues to pose a great challenge to global health, more effective and durable vaccines are needed owing to the waning protection offered by the current available vaccines. Here we report highly immunogenic self-assembling hepatitis B surface antigen (HBsAg) nanoparticles displaying the ectodomain of SARS-CoV-2 WA1 S6P, the prefusion spike stabilized by six proline substitutions. Three self-assembling nanoparticle constructs with different linkers named CL1, CL2 and CL3 expressed well-formed nanoparticles in mammalian cells. These purified nanoparticles can bind diverse monoclonal antibodies (mAbs) specific to different domains of SARS-CoV-2 spike. Immunization by DNA electroporation of CL2 and CL3 in mice elicited significantly more potent and durable neutralizing antibody responses against diverse SARS-CoV-2 strains than non-nanoparticle forms of stabilized spikes, including SARS-CoV-2 S2P and S6P ectodomain and full-length S2P with its coding sequence matching mRNA-1273. Our data showed that genetic delivery of HBsAg based nanoparticle vaccines displaying SARS-CoV-2 spike can elicit potent and durable neutralizing antibody responses and highlight their potential as next generation genetic vaccine candidates against SARS-CoV-2.
NIH Intramural Funding