iScience (Feb 2025)
MERS-CoV spike vaccine-induced N-terminal domain-specific antibodies are more protective than receptor binding domain-specific antibodies
- Olubukola M. Abiona,
- Nianshuang Wang,
- Sarah R. Leist,
- Alexandra Schäfer,
- Adam S. Cockrell,
- Lingshu Wang,
- Sandhya Bangaru,
- Laura Stevens,
- Rachel L. Graham,
- Jacob F. Kocher,
- Yaroslav Tsybovsky,
- Masaru Kanekiyo,
- Azad Kumar,
- Kaitlyn M. Morabito,
- Osnat Rosen,
- Wei Shi,
- Anne Werner,
- Yi Zhang,
- Cynthia Ziwawo,
- Christian K.O. Dzuvor,
- Charis Palandjian,
- Connor Eastman,
- Hannah R. Matthews,
- Jeswin Joseph,
- James D. Chappell,
- Wing-Pui Kong,
- John R. Mascola,
- Andrew B. Ward,
- Mark R. Denison,
- Ralph Baric,
- Jason S. McLellan,
- Barney S. Graham,
- Kizzmekia S. Corbett-Helaire
Affiliations
- Olubukola M. Abiona
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Nianshuang Wang
- Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
- Sarah R. Leist
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Alexandra Schäfer
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Adam S. Cockrell
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Lingshu Wang
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Sandhya Bangaru
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Laura Stevens
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37212, USA
- Rachel L. Graham
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Jacob F. Kocher
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Yaroslav Tsybovsky
- Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research Sponsored By the National Cancer Institute, Frederick, MD 21702, USA
- Masaru Kanekiyo
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Azad Kumar
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Kaitlyn M. Morabito
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Osnat Rosen
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Wei Shi
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Anne Werner
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Yi Zhang
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Cynthia Ziwawo
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Christian K.O. Dzuvor
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Charis Palandjian
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Connor Eastman
- Program in Virology, Harvard Medical School, Boston, MA 021115, USA
- Hannah R. Matthews
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Jeswin Joseph
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- James D. Chappell
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37212, USA
- Wing-Pui Kong
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- John R. Mascola
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Andrew B. Ward
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
- Mark R. Denison
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37212, USA
- Ralph Baric
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Jason S. McLellan
- Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA
- Barney S. Graham
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Kizzmekia S. Corbett-Helaire
- Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Corresponding author
- Journal volume & issue
-
Vol. 28,
no. 2
p. 111632
Abstract
Summary: 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_ΔRBD, 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.
