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Title: Evaluation of candidate vaccine approaches for MERS-CoV

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.
Authors:
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Publication Date:
Grant/Contract Number:
AC02-06CH11357; W-31-109-ENG-38
Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 6; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES
OSTI Identifier:
1214709

Wang, Lingshu, Shi, Wei, Joyce, M. Gordon, Modjarrad, Kayvon, Zhang, Yi, Leung, Kwanyee, Lees, Christopher R., Zhou, Tongqing, Yassine, Hadi M., Kanekiyo, Masaru, Yang, Zhi-yong, Chen, Xuejun, Becker, Michelle M., Freeman, Megan, Vogel, Leatrice, Johnson, Joshua C., Olinger, Gene, Todd, John P., Bagci, Ulas, Solomon, Jeffrey, Mollura, Daniel J., Hensley, Lisa, Jahrling, Peter, Denison, Mark R., Rao, Srinivas S., Subbarao, Kanta, Kwong, Peter D., Mascola, John R., Kong, Wing-Pui, and Graham, Barney S.. Evaluation of candidate vaccine approaches for MERS-CoV. United States: N. p., Web. doi:10.1038/ncomms8712.
Wang, Lingshu, Shi, Wei, Joyce, M. Gordon, Modjarrad, Kayvon, Zhang, Yi, Leung, Kwanyee, Lees, Christopher R., Zhou, Tongqing, Yassine, Hadi M., Kanekiyo, Masaru, Yang, Zhi-yong, Chen, Xuejun, Becker, Michelle M., Freeman, Megan, Vogel, Leatrice, Johnson, Joshua C., Olinger, Gene, Todd, John P., Bagci, Ulas, Solomon, Jeffrey, Mollura, Daniel J., Hensley, Lisa, Jahrling, Peter, Denison, Mark R., Rao, Srinivas S., Subbarao, Kanta, Kwong, Peter D., Mascola, John R., Kong, Wing-Pui, & Graham, Barney S.. Evaluation of candidate vaccine approaches for MERS-CoV. United States. doi:10.1038/ncomms8712.
Wang, Lingshu, Shi, Wei, Joyce, M. Gordon, Modjarrad, Kayvon, Zhang, Yi, Leung, Kwanyee, Lees, Christopher R., Zhou, Tongqing, Yassine, Hadi M., Kanekiyo, Masaru, Yang, Zhi-yong, Chen, Xuejun, Becker, Michelle M., Freeman, Megan, Vogel, Leatrice, Johnson, Joshua C., Olinger, Gene, Todd, John P., Bagci, Ulas, Solomon, Jeffrey, Mollura, Daniel J., Hensley, Lisa, Jahrling, Peter, Denison, Mark R., Rao, Srinivas S., Subbarao, Kanta, Kwong, Peter D., Mascola, John R., Kong, Wing-Pui, and Graham, Barney S.. 2015. "Evaluation of candidate vaccine approaches for MERS-CoV". United States. doi:10.1038/ncomms8712. https://www.osti.gov/servlets/purl/1214709.
@article{osti_1214709,
title = {Evaluation of candidate vaccine approaches for MERS-CoV},
author = {Wang, Lingshu and Shi, Wei and Joyce, M. Gordon and Modjarrad, Kayvon and Zhang, Yi and Leung, Kwanyee and Lees, Christopher R. and Zhou, Tongqing and Yassine, Hadi M. and Kanekiyo, Masaru and Yang, Zhi-yong and Chen, Xuejun and Becker, Michelle M. and Freeman, Megan and Vogel, Leatrice and Johnson, Joshua C. and Olinger, Gene and Todd, John P. and Bagci, Ulas and Solomon, Jeffrey and Mollura, Daniel J. and Hensley, Lisa and Jahrling, Peter and Denison, Mark R. and Rao, Srinivas S. and Subbarao, Kanta and Kwong, Peter D. and Mascola, John R. and Kong, Wing-Pui and Graham, Barney S.},
abstractNote = {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.},
doi = {10.1038/ncomms8712},
journal = {Nature Communications},
number = ,
volume = 6,
place = {United States},
year = {2015},
month = {7}
}