MERS-Coronavirus: From Discovery to Intervention

Identification: Haagmans, Bart



MERS-Coronavirus: From Discovery to Intervention
Bart L. Haaagmans1
1Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
Middle East respiratory syndrome coronavirus (MERS-CoV) was identified six years ago and continues to cause small outbreaks. Overall, more than 2000 cases in 27 countries, mainly in the Arabian Peninsula, have been reported to the WHO with a 35% case fatality rate. Accumulating serological and molecular evidence indicated that dromedary camels act as the reservoir for MERS-CoV. The circulation of the virus in these animals poses a continuous risk of virus spill-over to people in contact with camels, such as those working in slaughter houses and animal farms, evidenced by the presence of MERS-CoV antibodies in sera of those individuals in contact with dromedary camels. Therefore, it is of crucial importance to understand the biology of the virus and develop intervention measures. We identified the MERS-CoV receptor, dipeptidylpeptidase-4 (DPP4), using Fc-tagged fragments of the spike (S) protein in an immunoprecipitation assay followed by mass spectrometry. DPP4 is expressed in the lower respiratory tract of humans, consistent with the fact that humans may succumb to a lower respiratory tract infection. The viral S protein, a type I membrane glycoprotein that is assembled in trimers in the viral envelope, interacts with DPP4 through the S1 subunit. Neutralizing antibodies are almost solely directed against the receptor binding domain within the S1 subunit. We also demonstrated that a modified vaccinia virus Ankara virus vaccine expressing the MERS-CoV spike protein confers mucosal immunity in dromedary camels. Significant reduction of excreted infectious virus and viral RNA transcripts was observed in vaccinated animals upon MERS-CoV challenge as compared to controls. The MVA-S vectored vaccine may also be tested for protection of humans at risk, such as healthcare workers and people with camel contacts. In the end, such a One Health approach combining different efforts to target both humans and dromedaries may be needed to tackle this zoonotic outbreak.



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