Evaluation of candidate vaccine approaches for MERS-CoV

Lingshu Wang, Wei Shi, M. Gordon Joyce, Kayvon Modjarrad, Yi Zhang, Kwanyee Leung, Christopher R. Lees, Tongqing Zhou, Hadi M. Yassine, Masaru Kanekiyo, Zhi-yong Yang, Xuejun Chen, Michelle M. Becker, Megan Freeman, Leatrice Vogel, Joshua C. Johnson, Gene Olinger, John P. Todd, Ulas Bagci, Jeffrey Solomon, Daniel J. Mollura, Lisa Hensley, Peter Jahrling, Mark R. Denison, Srinivas S. Rao, Kanta Subbarao, Peter D. Kwong, John R. Mascola, Wing-Pui Kong () and Barney S. Graham ()
Additional contact information
Lingshu Wang: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Wei Shi: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
M. Gordon Joyce: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Kayvon Modjarrad: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Yi Zhang: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Kwanyee Leung: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Christopher R. Lees: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Tongqing Zhou: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Hadi M. Yassine: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Masaru Kanekiyo: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Zhi-yong Yang: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Xuejun Chen: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Michelle M. Becker: Vanderbilt University Medical Center
Megan Freeman: Vanderbilt University Medical Center
Leatrice Vogel: Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Joshua C. Johnson: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Gene Olinger: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health
John P. Todd: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Ulas Bagci: Center for Infectious Disease Imaging, National Institutes of Health
Jeffrey Solomon: Center for Infectious Disease Imaging, National Institutes of Health
Daniel J. Mollura: Center for Infectious Disease Imaging, National Institutes of Health
Lisa Hensley: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Peter Jahrling: Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Mark R. Denison: Vanderbilt University Medical Center
Srinivas S. Rao: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Kanta Subbarao: Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Peter D. Kwong: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
John R. Mascola: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Wing-Pui Kong: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Barney S. Graham: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

Date: 2015
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DOI: 10.1038/ncomms8712

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