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

Jing Tian ,Sarathi Boddapati,Robert Haupt,C Jason Wong,Holly Hammond,Stuart Weston,Bin Zhou,Gregory M Glenn ,Pedro A Piedra,Betty Ekechukwu,Rafia Khatoon,Louis Fries,James A Norton ,James F Papin ,Michael J Massare,Nita Patel,Matthew B Frieman,Małgorzata Wiśniewska ,Sonia Maciejewski,Mimi Guebre‐Xabier ,Larry Ellingsworth,Stefanie Kluepfel-Stahl,James Logue,Haixia Zhou,Kelsey Jacobson,Linda Stertman,Will Moffitt,Karin Bengtsson ,Alyse D Portnoff,Gale Smith

doi:10.1038/s41467-020-20653-8

Abstract

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).

Highlights

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
This is evident by western blot analysis with an anti-S2 specific antibody which shows both cleaved and uncleaved spike protein in partially purified membrane extracts
Having shown that vaccination with NVX-CoV2373/Matrix-M elicited multifunctional, antigen-specific, CD4+ T cell responses and virus-neutralizing antibodies in mice, we evaluated the effect of the immunization on germinal center (GC) formation by measuring the frequency of CD4+ T follicular helper (Tfh) and GC B cells in spleens

Summary

Introduction

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. 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. Low-dose levels of NVX-CoV2373 with Matrix-M was 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). These results support the clinical development of the NVX-CoV2373 vaccine for prevention of COVID-19 (NCT04368988)

Methods

Results

Conclusion