Evaluation of Candidate Vaccine Approaches for MERS-CoV

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 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*

Substances

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