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.

• Authors: 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, Barney S Graham
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 7712 (Jul 28 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 26218507 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Antibodies, Viral
• DNA, Viral
• Immunoglobulin G
• Spike Glycoprotein, Coronavirus
• Vaccines, DNA
• Viral Vaccines

Topics

• Animals
• Antibodies, Monoclonal (immunology)
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• Coronavirus Infections (prevention & control)
• DNA, Viral (immunology)
• Female
• HEK293 Cells
• Humans
• Immunoglobulin G (immunology)
• Macaca mulatta
• Male
• Mice
• Mice, Inbred BALB C
• Middle East Respiratory Syndrome Coronavirus (immunology)
• Spike Glycoprotein, Coronavirus (immunology)
• Vaccines, DNA (immunology)
• Viral Vaccines (immunology)