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

Tian, Jing-Hui; Patel, Nita; Haupt, Robert; Zhou, Haixia; Weston, Stuart; Hammond, Holly; Lague, 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; Wong, C. Jason; Piedra, Pedro A.; Frieman, Matthew B.; Massare, Michael J.; Fries, Louis; Lövgren Bengtsson, Karin; 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 immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).