Mark Denison
Last active: 2/22/2016

Evaluation of candidate vaccine approaches for MERS-CoV.

Wang L, Shi W, Joyce MG, Modjarrad K, Zhang Y, Leung K, Lees CR, Zhou T, Yassine HM, Kanekiyo M, Yang ZY, Chen X, Becker MM, Freeman M, Vogel L, Johnson JC, Olinger G, Todd JP, Bagci U, Solomon J, Mollura DJ, Hensley L, Jahrling P, Denison MR, Rao SS, Subbarao K, Kwong PD, Mascola JR, Kong WP, Graham BS
Nat Commun. 2015 6: 7712

PMID: 26218507 · PMCID: PMC4525294 · DOI: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 (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.

MeSH Terms (18)

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

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