Live-attenuated bivalent measles virus-derived vaccines targeting Middle East respiratory syndrome coronavirus induce robust and multifunctional T cell responses against both viruses in an appropriate mouse model

Bodmer, Bianca S.; Fiedler, Anna H.; Hanauer, Jan R.H.; Prüfer, Steffen; Mühlebach, Michael D.

Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to occur, making it one of the WHO´s targets for accelerated vaccine development. One vaccine candidate is based on live-attenuated measles virus (MV) vaccine encoding the MERS-CoV spike glycoprotein (MERS-S). MV(vac2)-MERS-S(H) induces robust humoral and cellular immunity against MERS-S mediating protection. Here, the induction and nature of immunity after vaccination with MV(vac2)-MERS-S(H) or novel MV(vac2)-MERS-N were further characterized. We focused on the necessity for vector replication and the nature of induced T cells, since functional CD8(+) T cells contribute importantly to clearance of MERS-CoV. While no immunity against MERS-CoV or MV was detected in MV-susceptible mice after immunization with UV-inactivated virus, replication-competent MV(vac2)-MERS-S(H) triggered robust neutralizing antibody titers also in adult mice. Furthermore, a significant fraction of MERS CoV-specific CD8(+) T cells and MV-specific CD4(+) T cells simultaneously expressing IFN-γ and TNF-α were induced, revealing that MV(vac2)-MERS-S(H) induces multifunctional cellular immunity.