New journal publication in Nature Communications!
Becker, M.C. Freeman, L.Vogel, J.C. Johnsson, G.Olinger, J.P.Todd, U. Bagci*
, J. Solomon, D.J. Mollura, L.Hansley, P. Jahriling, M.R. Denison, S.S.Rao, K.Subbarao, P.D.Kwong, J.R.Mascola, W.Kong, B.S. Graham,
Evaluation of Candidate Vaccine Approaches for MERS-CoV
Nature Communications, Volume 6, Article Number: 7712, 28 July 2015. http://doi.org/10.1038/ncomms8712
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 glycoprotein (S) 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 reveal that immunization elicits NAbs to the RBD, non-RBD portions of S1, and S2 subunit. Multiple neutralization mechanisms are demonstrated by solving the atomic structure of a NAb-RBD complex, sequencing of neutralization escape viruses, and constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed by computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.