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MERS-CoV spike vaccine-induced N-terminal domain-specific antibodies are more protective than receptor binding domain-specific antibodies

  1. Author:
    Abiona, Olubukola M
    Wang, Nianshuang
    Leist, Sarah R
    Schäfer, Alexandra
    Cockrell, Adam S
    Wang, Lingshu
    Bangaru, Sandhya
    Stevens, Laura
    Graham, Rachel L
    Kocher, Jacob F
    Tsybovsky,Yaroslav
    Kanekiyo, Masaru
    Kumar, Azad
    Morabito, Kaitlyn M
    Rosen, Osnat
    Shi, Wei
    Werner, Anne
    Zhang, Yi
    Ziwawo, Cynthia
    Dzuvor, Christian K O
    Palandjian, Charis
    Eastman, Connor
    Matthews, Hannah R
    Joseph, Jeswin
    Chappell, James D
    Kong, Wing-Pui
    Mascola, John R
    Ward, Andrew B
    Denison, Mark R
    Baric, Ralph
    McLellan, Jason S
    Graham, Barney S
    Corbett-Helaire, Kizzmekia S

  2. Author Address

    Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA., Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37212, USA., Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored By the National Cancer Institute, Frederick, MD 21702, USA., Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Program in Virology, Harvard Medical School, Boston, MA 021115, USA., Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.,
    1. Year: 2025
    2. Date: Feb 21
    3. Epub Date: 2024 12 18
  2. Journal: iScience
    1. 28
    2. 2
    3. Pages: 111632
  4. Type of Article: Article
  5. Article Number: 111632
  1. Abstract:

    The COVID-19 pandemic underscores the need to prepare for future emerging coronavriuses (CoVs) by understanding the principles behind effective CoV vaccine design such as protective immunity and antibody responses. To study which epitopes and subdomains contribute to in vivo protection, we utilized the prefusion-stabilized spike protein of MERS-CoV, MERS S-2P, as a vaccine immunogen. Vaccination with MERS S-2P elicited both receptor-binding domain (RBD)- and non-RBD-specific antibodies, including N-terminal domain (NTD)-specific G2-and CDC2-A2-like antibodies. Intriguingly, the immunogen MERS S-2P_?RBD, MERS S-2P with the RBDs removed, protects comparably to S1 and S-2P immunogens against MERS-CoV challenge. Moreover, passive transfer studies of polyclonal IgG from MERS S-2P immunized mice depleted of subdomain-specific antibodies demonstrated that non-RBD antibodies protected more than non-NTD antibodies. Altogether, these findings illustrate that in-vivo protection is not solely driven by RBD-specific antibodies and highlights the importance of targeting non-RBD sites in future CoV vaccine designs. © 2024 The Author(s).

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External Sources

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  2. DOI: 10.1016/j.isci.2024.111632
  3. PMID: 39898019
  4. PMCID: PMC11783452
  5. PII : S2589-0042(24)02859-1

Library Notes

  1. Fiscal Year: FY2024-2025
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