Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein

摘要

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoralimmune response was induced after the animal had been vaccinated with themembrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of theglycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizingantibodies among all vaccinated animals. The most significant cellular immuneresponse was induced after vaccination of the animals with the full-length S(rAd5-S). These investigations suggest that the full-length S and the membraneform of the RBD (RBD-G) are the most promising vaccine candidates among all thestudied forms of S glycoprotein.