SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice.
Author
Tian, Jing-HuiPatel, Nita
Haupt, Robert
Zhou, Haixia
Weston, Stuart
Hammond, Holly
Logue, James
Portnoff, Alyse D
Norton, James
Guebre-Xabier, Mimi
Zhou, Bin
Jacobson, Kelsey
Maciejewski, Sonia
Khatoon, Rafia
Wisniewska, Malgorzata
Moffitt, Will
Kluepfel-Stahl, Stefanie
Ekechukwu, Betty
Papin, James
Boddapati, Sarathi
Jason Wong, C
Piedra, Pedro A
Frieman, Matthew B
Massare, Michael J
Fries, Louis
Bengtsson, Karin Lövgren
Stertman, Linda
Ellingsworth, Larry
Glenn, Gregory
Smith, Gale
Date
2021-01-14Journal
Nature CommunicationsPublisher
Springer NatureType
Article
Metadata
Show full item recordAbstract
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).Identifier to cite or link to this item
http://hdl.handle.net/10713/14410ae974a485f413a2113503eed53cd6c53
10.1038/s41467-020-20653-8
Scopus Count
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