Live-attenuated measles/mumps vaccine(Wuhan Institute of Biological Products Co., Ltd.)

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.

Herein we present a novel molecular mechanism of the antitumor effects of live-attenuated measles virus (MV) vaccine in ovarian cancer. Using a 2-DE/MS-based comparative proteomics strategy, we identified 17 proteins differentially expressed in live-attenuated MV vaccine-treated SKOV-3 ovarian cancer cells, including oxidative stress-associated enzymes and cell contact-related proteins, which indicated that live-attenuated MV vaccine could induce aberrant ROS activation. It further mediated epigenetic silencing of E-cadherin via upregulating DNMT3a that conferred both cell-cell and cell-matrix contact loss and apoptosis of ovarian cancer cells. This process could be reversed through ROS inhibition. Our study lays the theoretical foundation for the clinical application of live-attenuated MV vaccine as a potential oncotherapeutic agent for ovarian cancer treatment.