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

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    Author
    Tian, Jing-Hui
    Patel, Nita
    Haupt, Robert
    Zhou, Haixia
    Weston, Stuart
    Hammond, Holly
    Logue, James
    Portnoff, Alyse D
    Norton, James
    Guebre-Xabier, Mimi
    Zhou, Bin
    Jacobson, Kelsey
    Maciejewski, Sonia
    Khatoon, Rafia
    Wisniewska, Malgorzata
    Moffitt, Will
    Kluepfel-Stahl, Stefanie
    Ekechukwu, Betty
    Papin, James
    Boddapati, Sarathi
    Jason Wong, C
    Piedra, Pedro A
    Frieman, Matthew B
    Massare, Michael J
    Fries, Louis
    Bengtsson, Karin Lövgren
    Stertman, Linda
    Ellingsworth, Larry
    Glenn, Gregory
    Smith, Gale
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    Date
    2021-01-14
    Journal
    Nature Communications
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/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).
    Keyword
    NVX-CoV2373
    COVID-19
    SARS-CoV-2
    COVID-19 Vaccines
    Mice
    Papio
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/14410
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-020-20653-8
    Scopus Count
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    UMB Coronavirus Publications

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