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

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-020-20653-8

2041-1723

Jing-Hui Tian, Nita Patel, Robert Haupt, Haixia Zhou, Stuart Weston, Holly Hammond, James Logue, Alyse D. Portnoff, James A. Norton, Mimi Guebre‐Xabier, Bin Zhou, Kelsey Jacobson, Sonia Maciejewski, Rafia Khatoon, Marzenna Wiśniewska, Will Moffitt, Stefanie Kluepfel-Stahl, Betty Ekechukwu, James F. 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 M. Glenn, Gale Smith,

Animal Virus Infections Studies

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).