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Nat Commun. 2015 Jul 28;6:7712. doi: 10.1038/ncomms8712.

Evaluation of candidate vaccine approaches for MERS-CoV.

Author information

1
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
2
1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2] U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA [3] Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland 20817, USA.
3
1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Sanofi-Aventis, 270 Albany Street, Cambridge, Massachusetts 02139, USA.
4
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
5
Emerging Respiratory Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
6
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland,21702, USA.
7
1] Center for Infectious Disease Imaging, Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Center for Research in Computer Vision (CRCV), University of Central Florida, Orlando, Florida 32816, USA.
8
Center for Infectious Disease Imaging, Department of Radiology and Imaging Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA.
9
1] Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA [2] Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

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.

PMID:
26218507
PMCID:
PMC4525294
DOI:
10.1038/ncomms8712
[Indexed for MEDLINE]
Free PMC Article

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