SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice

Tian, J.-H.; Patel, N.; Haupt, R.; Zhou, H.; Weston, S.; Hammond, H.; Lague, J.; Portnoff, A. D.; Norton, J.; Guebre-Xabier, M.; Zhou, B.; Jacobson, K.; Maciejewski, S.; Khatoon, R.; Wisniewska, M.; Mottitt, W.; Kluepfel-Stahl, S.; Ekechukwu, B.; Papin, J.; Boddapati, S.; Wong, C. J.; Piedra, P. A.; Frieman, M. B.; Massare, M. J.; Fries, L.; Lovgren Bengtsson, K.; Stertman, L.; Ellingsworth, L. R.; Glenn, G.; Smith, G.

doi:10.1101/2020.06.29.178509

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bioRxiv · 10.1101/2020.06.29.178509

SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice

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Abstract

The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).

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Tian, J.-H., Patel, N., Haupt, R., Zhou, H., Weston, S., Hammond, H., Lague, J., Portnoff, A. D., Norton, J., Guebre-Xabier, M., Zhou, B., Jacobson, K., Maciejewski, S., Khatoon, R., Wisniewska, M., Mottitt, W., Kluepfel-Stahl, S., Ekechukwu, B., Papin, J., Boddapati, S., Wong, C. J., Piedra, P. A., Frieman, M. B., Massare, M. J., Fries, L., Lovgren Bengtsson, K., Stertman, L., Ellingsworth, L. R., Glenn, G., Smith, G.. 2020-06-30. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice. https://doi.org/10.1101/2020.06.29.178509

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