1. 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
- Author
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Bianca S. Bodmer, Steffen Prüfer, Jan R.H. Hanauer, Michael D. Mühlebach, and Anna H. Fiedler
- Subjects
0301 basic medicine ,Cellular immunity ,MERS Coronavirus ,viruses ,T cell ,Measles Virus ,CD8-Positive T-Lymphocytes ,Antibodies, Viral ,Vaccines, Attenuated ,Article ,Virus ,Measles virus ,03 medical and health sciences ,Immunity ,Virology ,medicine ,Animals ,Neutralizing antibody ,Immunity, Cellular ,Mice, Inbred BALB C ,biology ,Viral Vaccines ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Antibodies, Neutralizing ,Vaccination ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Vaccine platform ,Spike Glycoprotein, Coronavirus ,Middle East Respiratory Syndrome Coronavirus ,biology.protein ,Antibody responses ,Multifunctional T cells ,Coronavirus Infections ,CD8 - Abstract
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). MVvac2-MERS-S(H) induces robust humoral and cellular immunity against MERS-S mediating protection. Here, the induction and nature of immunity after vaccination with MVvac2-MERS-S(H) or novel MVvac2-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 MVvac2-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 MVvac2-MERS-S(H) induces multifunctional cellular immunity., Highlights • Measles vaccine virus encoding MERS-CoV N induce N-specific T ell responses. • Only live recombinant vaccine triggers immunity. • MERS-vaccine candidates work also in adult animals. • Multifunctional antigen-specific T cells targeting MERS-S are induced by recombinant MVvac2-MERS-S(H).
- Published
- 2018