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

Abstract

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

• Authors: Jing-Hui Tian, Nita Patel, Robert Haupt, Haixia Zhou, Stuart Weston, Holly Hammond, James Logue, Alyse D Portnoff, James Norton, Mimi Guebre-Xabier, Bin Zhou, Kelsey Jacobson, Sonia Maciejewski, Rafia Khatoon, Malgorzata Wisniewska, Will Moffitt, Stefanie Kluepfel-Stahl, Betty Ekechukwu, James Papin, Sarathi Boddapati, C Jason Wong, Pedro A Piedra, Matthew B Frieman, Michael J Massare, Louis Fries, Karin Lövgren Bengtsson, Linda Stertman, Larry Ellingsworth, Gregory Glenn, Gale Smith
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 372 (01 14 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 33446655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19 Vaccines
• Spike Glycoprotein, Coronavirus
• Vaccines, Subunit
• spike protein, SARS-CoV-2
• Angiotensin-Converting Enzyme 2

Topics

• Angiotensin-Converting Enzyme 2 (genetics, immunology)
• Animals
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• COVID-19 (genetics, immunology, prevention & control, virology)
• COVID-19 Vaccines (administration & dosage, genetics, immunology)
• Disease Models, Animal
• Female
• Male
• Mice
• Mice, Inbred BALB C
• Papio
• SARS-CoV-2 (genetics, immunology)
• Spike Glycoprotein, Coronavirus (administration & dosage, genetics, immunology)
• T-Lymphocytes (immunology)
• Vaccines, Subunit (administration & dosage, genetics, immunology)