@article{601333d633b94b4fa180be6b5136c017,
title = "Evaluation of candidate vaccine approaches for MERS-CoV",
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.",
author = "Lingshu Wang and Wei Shi and Joyce, {M. Gordon} and Kayvon Modjarrad and Yi Zhang and Kwanyee Leung and Lees, {Christopher R.} and Tongqing Zhou and Yassine, {Hadi M.} and Masaru Kanekiyo and Yang, {Zhi Yong} and Xuejun Chen and Becker, {Michelle M.} and Megan Freeman and Leatrice Vogel and Johnson, {Joshua C.} and Gene Olinger and Todd, {John P.} and Ulas Bagci and Jeffrey Solomon and Mollura, {Daniel J.} and Lisa Hensley and Peter Jahrling and Denison, {Mark R.} and Rao, {Srinivas S.} and Kanta Subbarao and Kwong, {Peter D.} and Mascola, {John R.} and Kong, {Wing Pui} and Graham, {Barney S.}",
note = "Funding Information: We thank members of the Viral Pathogenesis and Virology Laboratories as well as the Structural Biology and Structural Bioinformatics Sections at the Vaccine Research Center for insightful comments and helpful discussions. We also thank Brenda Hartman and Jonathon Stuckey for their assistance in preparing the figures. The data presented in this manuscript are tabulated in the main paper and the Supplementary Materials. Atomic coordinates and structure factors of the reported crystal structures have been deposited in the Protein Data Bank under accession codes 4ZPT, 4ZPV and 4ZPW. This work was supported by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH. Use of sector 22 (SER-CAT) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract number W-31-109-Eng-38. M.R.D, and M.M.B. were supported by RO1-AI-108197. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, NRC Publication, 2011 edition. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = jul,
day = "28",
doi = "10.1038/ncomms8712",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}
