Intranasal vaccination with recombinant receptor-binding domain ofMERS-CoV spike protein induces much stronger local mucosalimmune responses than subcutaneous immunization: Implication fordesigning novel mucosal MERS vaccines

tMiddle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was originally identified in SaudiArabia in 2012. It has caused MERS outbreaks with high mortality in the Middle East and Europe, raisinga serious concern about its pandemic potential. Therefore, development of effective vaccines is crucialfor preventing its further spread and future pandemic. Our previous study has shown that subcutaneous(s.c.) vaccination of a recombinant protein containing receptor-binding domain (RBD) of MERS-CoV Sfused with Fc of human IgG (RBD-Fc) induced strong systemic neutralizing antibody responses in vacci-nated mice. Here, we compared local and systemic immune responses induced by RBD-Fc via intranasal(i.n.) and s.c. immunization pathways. We found that i.n. vaccination of MERS-CoV RBD-Fc induced sys-temic humoral immune responses comparable to those induced by s.c. vaccination, including neutralizingantibodies, but more robust systemic cellular immune responses and significantly higher local mucosalimmune responses in mouse lungs. This study suggests the potential of developing MERS-CoV RBD pro-tein into an effective and safe mucosal candidate vaccine for prevention of respiratory tract infectionscaused by MERS-CoV.