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SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice.
Nat Commun. 2021 01 14; 12(1):372.NC

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).

Authors+Show Affiliations

Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Department of Pathology, Division of Comparative Medicine, University of Oklahoma, Health Sciences Center, 940 Stanton L. Young, BMS 203, Oklahoma City, OK, 73104, USA.Catalent Cell & Gene Therapy, 20 Firstfield Road, Gaithersburg, MD, 20874, USA.Catalent Cell & Gene Therapy, 20 Firstfield Road, Gaithersburg, MD, 20874, USA.Department of Molecular Virology and Microbiology, and Pediatrics, Baylor College of Medicine, Houston, TX, USA.University of Maryland, School of Medicine, 685 West Baltimore St, Baltimore, MD, 21201, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax AB, Kungsgatan 109, SE-753 18, Uppsala, Sweden.Novavax AB, Kungsgatan 109, SE-753 18, Uppsala, Sweden.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA.Novavax, Inc., 21 Firstfield Road, Gaithersburg, MD, 20878, USA. GSmith@Novavax.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33446655

Citation

Tian, Jing-Hui, et al. "SARS-CoV-2 Spike Glycoprotein Vaccine Candidate NVX-CoV2373 Immunogenicity in Baboons and Protection in Mice." Nature Communications, vol. 12, no. 1, 2021, p. 372.
Tian JH, Patel N, Haupt R, et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun. 2021;12(1):372.
Tian, J. H., Patel, N., Haupt, R., Zhou, H., Weston, S., Hammond, H., Logue, J., Portnoff, A. D., Norton, J., Guebre-Xabier, M., Zhou, B., Jacobson, K., Maciejewski, S., Khatoon, R., Wisniewska, M., Moffitt, W., Kluepfel-Stahl, S., Ekechukwu, B., Papin, J., ... Smith, G. (2021). SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nature Communications, 12(1), 372. https://doi.org/10.1038/s41467-020-20653-8
Tian JH, et al. SARS-CoV-2 Spike Glycoprotein Vaccine Candidate NVX-CoV2373 Immunogenicity in Baboons and Protection in Mice. Nat Commun. 2021 01 14;12(1):372. PubMed PMID: 33446655.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. AU - Tian,Jing-Hui, AU - Patel,Nita, AU - Haupt,Robert, AU - Zhou,Haixia, AU - Weston,Stuart, AU - Hammond,Holly, AU - Logue,James, AU - Portnoff,Alyse D, AU - Norton,James, AU - Guebre-Xabier,Mimi, AU - Zhou,Bin, AU - Jacobson,Kelsey, AU - Maciejewski,Sonia, AU - Khatoon,Rafia, AU - Wisniewska,Malgorzata, AU - Moffitt,Will, AU - Kluepfel-Stahl,Stefanie, AU - Ekechukwu,Betty, AU - Papin,James, AU - Boddapati,Sarathi, AU - Jason Wong,C, AU - Piedra,Pedro A, AU - Frieman,Matthew B, AU - Massare,Michael J, AU - Fries,Louis, AU - Bengtsson,Karin Lövgren, AU - Stertman,Linda, AU - Ellingsworth,Larry, AU - Glenn,Gregory, AU - Smith,Gale, Y1 - 2021/01/14/ PY - 2020/06/30/received PY - 2020/12/08/accepted PY - 2021/1/15/entrez PY - 2021/1/16/pubmed PY - 2021/1/20/medline SP - 372 EP - 372 JF - Nature communications JO - Nat Commun VL - 12 IS - 1 N2 - 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). SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/33446655/SARS_CoV_2_spike_glycoprotein_vaccine_candidate_NVX_CoV2373_immunogenicity_in_baboons_and_protection_in_mice_ L2 - https://doi.org/10.1038/s41467-020-20653-8 DB - PRIME DP - Unbound Medicine ER -