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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.
Hospitalized children < 2 years of age in Amman, Jordan, admitted for fever and/or respiratory symptoms, were tested for Middle East respiratory syndrome coronavirus (MERS-CoV): MERS-CoV by real-time RT-PCR (rRT-PCR). This was a prospective year-round viral surveillance study in children <2 years of age admitted with acute respiratory symptoms and/or fever from March 2010 to September 2012 and enrolled from a government-run hospital, Al-Bashir in Amman, Jordan. Clinical and demographic data, including antibiotic use, were collected. Combined nasal/throat swabs were collected, aliquoted, and frozen at -80°C. Specimen aliquots were shipped to Vanderbilt University and the Centers for Disease Control and Prevention (CDC), and tested by rRT-PCR for MERS-CoV. Of the 2433 subjects enrolled from 16 March 2010 to 10 September 2012, 2427 subjects had viral testing and clinical data. Of 1898 specimens prospectively tested for other viruses between 16 March 2010 and 18 March 2012, 474 samples did not have other common respiratory viruses detected. These samples were tested at CDC for MERS-CoV and all were negative by rRT-PCR for MERS-CoV. Of the remaining 531 samples, collected from 19 March 2012 to 10 September 2012 and tested at Vanderbilt, none were positive for MERS-CoV. Our negative findings from a large sample of young Jordanian children hospitalized with fever and/or respiratory symptoms suggest that MERS-CoV was not widely circulating in Amman, Jordan, during the 30-month period of prospective, active surveillance occurring before and after the first documented MERS-CoV outbreak in the Middle East region.
© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.