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 SolomonDaniel 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

240 Scopus citations

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.

Original languageEnglish (US)
Article number7712
JournalNature communications
Volume6
DOIs
StatePublished - Jul 28 2015
Externally publishedYes

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Evaluation of candidate vaccine approaches for MERS-CoV'. Together they form a unique fingerprint.

Cite this