MERS-CoV spike vaccine-induced N-terminal domain-specific antibodies are more protective than receptor binding domain-specific antibodies
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 <i>in vivo</i> 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 <i>in-vivo</i> protection is not solely driven by RBD-specific antibodies and highlights the importance of targeting non-RBD sites in future CoV vaccine designs.
Authors
- Andrew C. Ward (ORCID: https://orcid.org/0000-0002-5302-5899)
- Jason S. McLellan (ORCID: https://orcid.org/0000-0003-3991-542X)
- Anne P. Werner (ORCID: https://orcid.org/0000-0003-2322-6830)
- Cynthia T. Ziwawo (ORCID: https://orcid.org/0000-0002-9772-8123)
- Adam S. Cockrell
- Ralph Steven Baric (ORCID: https://orcid.org/0000-0001-6827-8701)
- Osnat Rosen (ORCID: https://orcid.org/0000-0001-7604-1755)
- Barney S. Graham (ORCID: https://orcid.org/0000-0001-8112-0853)
- Kizzmekia S. Corbett (ORCID: https://orcid.org/0000-0002-2641-4688)
- Rachel L. Graham (ORCID: https://orcid.org/0000-0002-3143-6515)
- Sandhya Bangaru (ORCID: https://orcid.org/0000-0001-7994-4693)
- Azad Kumar
- Wing‐Pui Kong (ORCID: https://orcid.org/0000-0001-8544-6447)
- Joseph Jeswin
- Kaitlyn M. Morabito (ORCID: https://orcid.org/0000-0002-4849-4690)
- Sarah R. Leist (ORCID: https://orcid.org/0000-0002-4989-5381)
- Masaru Kanekiyo (ORCID: https://orcid.org/0000-0001-5767-1532)
- Laura J. Stevens (ORCID: https://orcid.org/0000-0003-4386-6958)
- Jacob Kocher (ORCID: https://orcid.org/0000-0001-6768-3449)
- Olubukola M. Abiona (ORCID: https://orcid.org/0000-0002-2745-1691)
- Yaroslav Tsybovsky (ORCID: https://orcid.org/0000-0002-2159-5248)
- Nianshuang Wang (ORCID: https://orcid.org/0000-0002-7569-011X)
- Wei Shi (ORCID: https://orcid.org/0000-0002-7065-4654)
- Charis Palandjian
- James D. Chappell (ORCID: https://orcid.org/0000-0002-7382-7864)
- Lingshu Wang (ORCID: https://orcid.org/0000-0001-5263-3633)
- Helen Matthews
- Mark R. Denison
- John R. Mascola
- Alexandra Schäfer
- Christian K O Dzuvor
- Connor Eastman
- Yi Zhang (ORCID: https://orcid.org/0000-0001-6223-4724)
Institutions
- University of North Carolina at Chapel Hill (US)
- Scripps Research Institute (US)
- National Institutes of Health (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- Frederick National Laboratory for Cancer Research (US)
- National Institute of Allergy and Infectious Diseases (US)
- The University of Texas at Austin (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- iScience
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1016/j.isci.2024.111632
- Citations
- 4
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.56
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Harvard T.H. Chan School of Public Health
- Leidos
- Vaccine Research Center
- National Institutes of Health
- NIH Office of the Director
- National Institute of Allergy and Infectious Diseases
- Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases