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
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
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DOI：
10.1016/j.virol.2018.05.028
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发表时间：
2018-08-01
期刊：
影响因子：
3.7
通讯作者：
Muehlebach, Michael D.
中科院分区：
文献类型：
--
作者：
Bodmer, Bianca S.;Fiedler, Anna H.;Muehlebach, Michael D.
中东呼吸综合征冠状病毒（MERS-CoV）病例继续发生，使其成为世卫组织加速疫苗开发的目标之一。一种候选疫苗是基于编码MERS-CoV刺突糖蛋白（MERS-S）的减毒活麻疹病毒（MV）疫苗。MVvac 2-MERS-S（H）诱导针对MERS-S介导的保护的稳健的体液和细胞免疫。在此，进一步表征了用MVvac 2-MERS-S（H）或新型MVvac 2-MERS-N接种后免疫的诱导和性质。我们重点关注载体复制的必要性和诱导T细胞的性质，因为功能性CD 8（+）T细胞对MERS-CoV的清除有重要贡献。虽然在用UV灭活病毒免疫后，在MV易感小鼠中未检测到针对MERS-CoV或MV的免疫力，但具有复制能力的MVvac 2-MERS-S（H）也在成年小鼠中引发了稳健的中和抗体滴度。此外，诱导了显著部分的同时表达IFN-γ和TNF-α的MERS CoV特异性CD 8（+）T细胞和MV特异性CD 4（+）T细胞，揭示了MVvac 2-MERS-S（H）诱导多功能细胞免疫。
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-gamma and TNF-alpha were induced, revealing that MVvac2-MERS-S(H) induces multifunctional cellular immunity.