January 14, 2021

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

NIS Mountain Hero

Researchers show that a full-length, stabilized prefusion SARS-CoV-2 S glycoprotein vaccine (NVX-CoV2373) adjuvanted by Matrix-M can induce high levels of functional immunity in mice and baboons, and protects mice expressing hACE2 receptors in a live SARS-CoV-2 challenge. The functional immunity induced by this nanoparticle vaccine and Matrix-M adjuvant clearly depends on both the adjuvant and antigen components and mirrors the human experience with influenza hemagglutinin vaccine and a naïve population with Ebola recombinant protein nanoparticle vaccines.

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).


Tian, JH., Patel, N., Haupt, R. et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun 12, 372 (2021). https://doi.org/10.1038/s41467-020-20653-8

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 L�vgren Bengtsson, Linda Stertman, Larry Ellingsworth, Gregory Glenn & Gale Smith
NIS Mountain Hero