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

Tian, Jing-Hui; Patel, 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

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).