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

Author

Listed:
  • Jing-Hui Tian

    (Novavax, Inc.)

  • Nita Patel

    (Novavax, Inc.)

  • Robert Haupt

    (University of Maryland, School of Medicine)

  • Haixia Zhou

    (Novavax, Inc.)

  • Stuart Weston

    (University of Maryland, School of Medicine)

  • Holly Hammond

    (University of Maryland, School of Medicine)

  • James Logue

    (University of Maryland, School of Medicine)

  • Alyse D. Portnoff

    (Novavax, Inc.)

  • James Norton

    (Novavax, Inc.)

  • Mimi Guebre-Xabier

    (Novavax, Inc.)

  • Bin Zhou

    (Novavax, Inc.)

  • Kelsey Jacobson

    (Novavax, Inc.)

  • Sonia Maciejewski

    (Novavax, Inc.)

  • Rafia Khatoon

    (Novavax, Inc.)

  • Malgorzata Wisniewska

    (Novavax, Inc.)

  • Will Moffitt

    (Novavax, Inc.)

  • Stefanie Kluepfel-Stahl

    (Novavax, Inc.)

  • Betty Ekechukwu

    (Novavax, Inc.)

  • James Papin

    (University of Oklahoma, Health Sciences Center)

  • Sarathi Boddapati

    (Catalent Cell & Gene Therapy)

  • C. Jason Wong

    (Catalent Cell & Gene Therapy)

  • Pedro A. Piedra

    (Baylor College of Medicine)

  • Matthew B. Frieman

    (University of Maryland, School of Medicine)

  • Michael J. Massare

    (Novavax, Inc.)

  • Louis Fries

    (Novavax, Inc.)

  • Karin Lövgren Bengtsson

    (Novavax AB)

  • Linda Stertman

    (Novavax AB)

  • Larry Ellingsworth

    (Novavax, Inc.)

  • Gregory Glenn

    (Novavax, Inc.)

  • Gale Smith

    (Novavax, Inc.)

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).

Suggested Citation

  • Jing-Hui Tian & Nita Patel & Robert Haupt & Haixia Zhou & Stuart Weston & Holly Hammond & James Logue & Alyse D. Portnoff & James Norton & Mimi Guebre-Xabier & Bin Zhou & Kelsey Jacobson & Sonia Macie, 2021. "SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20653-8
    DOI: 10.1038/s41467-020-20653-8
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    Cited by:

    1. Eike-Christian Wamhoff & Larance Ronsard & Jared Feldman & Grant A. Knappe & Blake M. Hauser & Anna Romanov & James Brett Case & Shilpa Sanapala & Evan C. Lam & Kerri J. St. Denis & Julie Boucau & Amy, 2024. "Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Cai He & Jingyun Yang & Weiqi Hong & Zimin Chen & Dandan Peng & Hong Lei & Aqu Alu & Xuemei He & Zhenfei Bi & Xiaohua Jiang & Guowen Jia & Yun Yang & Yanan Zhou & Wenhai Yu & Cong Tang & Qing Huang & , 2022. "A self-assembled trimeric protein vaccine induces protective immunity against Omicron variant," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Ravindra B. Malabadi & Neelambika T. Meti & Raju K. Chalannavar, 2021. "Applications of nanotechnology in vaccine development for coronavirus (SARS-CoV-2) disease (Covid-19)," International Journal of Research and Scientific Innovation, International Journal of Research and Scientific Innovation (IJRSI), vol. 8(2), pages 191-198, February.
    4. Jimin Lee & Cameron Stewart & Alexandra Schäfer & Elizabeth M. Leaf & Young-Jun Park & Daniel Asarnow & John M. Powers & Catherine Treichel & Kaitlin R. Sprouse & Davide Corti & Ralph Baric & Neil P. , 2024. "A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Rafael R. G. Machado & Jordyn L. Walker & Dionna Scharton & Grace H. Rafael & Brooke M. Mitchell & Rachel A. Reyna & William M. Souza & Jianying Liu & David H. Walker & Jessica A. Plante & Kenneth S. , 2023. "Immunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Ravindra B. Malabadi & Neelambika T. Meti & Raju K. Chalannavar, 2021. "Role of herbal medicine for controlling coronavirus (SARS-CoV-2) disease (COVID-19)," International Journal of Research and Scientific Innovation, International Journal of Research and Scientific Innovation (IJRSI), vol. 8(2), pages 135-165, February.
    7. James Logue & Robert M. Johnson & Nita Patel & Bin Zhou & Sonia Maciejewski & Bryant Foreman & Haixia Zhou & Alyse D. Portnoff & Jing-Hui Tian & Asma Rehman & Marisa E. McGrath & Robert E. Haupt & Stu, 2023. "Immunogenicity and protection of a variant nanoparticle vaccine that confers broad neutralization against SARS-CoV-2 variants," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Eakachai Prompetchara & Chutitorn Ketloy & Mohamad-Gabriel Alameh & Kittipan Tharakhet & Papatsara Kaewpang & Nongnaphat Yostrerat & Patrawadee Pitakpolrat & Supranee Buranapraditkun & Suwimon Manopwi, 2023. "Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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