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.
【저자키워드】 Protein vaccines, 【초록키워드】 SARS-CoV-2, Vaccine, immunogenicity, antibody, T cells, COVID-19 pandemic, virus, CD4, CD8, Spike protein, hACE2, Antigen, B cell, Spread, Protein, Antigen-specific T cells, clinical evaluation, mice, low-dose, Respiratory disease, vaccine candidate, Germinal center, Subunit vaccine, receptor, virus infection, respiratory, spleen, Protein binding, Protective, binding, Tfh, anti-S IgG, Evidence, S-protein, angiotensin, Safe, NVX-CoV2373, evidence of, no evidence of, Support, Saponin, subunit, enzyme, human Angiotensin-converting enzyme, high affinity, hACE2 receptor, immunogenic, full-length spike protein, full-length, prefusion conformation, anti-S antibody, block, neutralize, helper T cell, Matrix-M, PROTECT, functional, elicit, elicited, multifunctional, follicular, 【제목키워드】 SARS-CoV-2 spike glycoprotein, vaccine candidate,