Jing-Hui Tian 1 , Nita Patel 1 , Robert Haupt 2 , Haixia Zhou 1 , Stuart Weston 2 , Holly Hammond 2 , James Logue 2 , Alyse D. Portnoff 1 , James Norton 1 , Mimi Guebre-Xabier 1 , Bin Zhou 1 , Kelsey Jacobson 1 , Sonia Maciejewski 1 , Rafia Khatoon 1 , Malgorzata Wisniewska 1 , Will Moffitt 1 , Stefanie Kluepfel-Stahl 1 , Betty Ekechukwu 1 , James Papin 3 , Sarathi Boddapati 4 , C. Jason Wong 4 , Pedro A. Piedra 5 , Matthew B. Frieman 2 , Michael J. Massare 1 , Louis Fries 1 , Karin Lövgren Bengtsson 6 , Linda Stertman 6 , Larry Ellingsworth 1 , Gregory Glenn 1 , Gale Smith , 1
14 January 2021
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).
Here, the authors characterize a SARS-CoV-2 subunit vaccine candidate that contains full-length spike protein stabilized in its prefusion conformation, and show immunogenicity in baboons and protection in mice with Matrix-M adjuvanted vaccine.