Journal Article

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

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

2021

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250/590/2294 / 631/61/24/590/2294 / 82/1 / 82/80 / 82/83 / ACE2 / Angiotensin / Angiotensin-converting enzyme 2 / Angiotensin-Converting Enzyme 2 - genetics / Angiotensin-Converting Enzyme 2 - immunology / Animals / Antibodies / Antibodies, Neutralizing - immunology / Antibodies, Viral - immunology / Antigens / Baboons / Binding / CD4 antigen / CD8 antigen / COVID-19 / COVID-19 - genetics / COVID-19 - immunology / COVID-19 - prevention & control / COVID-19 - virology / COVID-19 Vaccines - administration & dosage / COVID-19 Vaccines - genetics / COVID-19 Vaccines - immunology / Disease control / Disease Models, Animal / Female / Glycoproteins / Humanities and Social Sciences / Immunogenicity / Immunoglobulin G / Lymphocytes / Lymphocytes B / Lymphocytes T / Male / Mice / Mice, Inbred BALB C / multidisciplinary / Nanoparticles / Pandemics / Papio / Peptidyl-dipeptidase A / Proteins / Receptors / Respiratory diseases / Saponins / SARS-CoV-2 - genetics / SARS-CoV-2 - immunology / Science / Science (multidisciplinary) / Severe acute respiratory syndrome coronavirus 2 / Spike glycoprotein / Spike Glycoprotein, Coronavirus - administration & dosage / Spike Glycoprotein, Coronavirus - genetics / Spike Glycoprotein, Coronavirus - immunology / Spike protein / Spleen / T-Lymphocytes - immunology / Vaccines / Vaccines, Subunit - administration & dosage / Vaccines, Subunit - genetics / Vaccines, Subunit - immunology / Viral diseases / Viruses