Tomić Adriana, Varanasi Pavankumar R, Golemac Mijo, Malić Suzana, Riese Peggy, Borst Eva M, Mischak-Weissinger Eva, Guzmán Carlos A, Krmpotić Astrid, Jonjić Stipan, Messerle Martin
Institute of Virology, Hannover Medical School, Hannover, Germany.
Clinics of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
PLoS Pathog. 2016 Dec 1;12(12):e1006015. doi: 10.1371/journal.ppat.1006015. eCollection 2016 Dec.
Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells. Infection with the ULBP2-expressing HCMV strain caused diminished cell surface levels of MHC class I molecules. While expression of the NKG2D ligand increased the cytolytic activity of NK cells, NKG2D engagement in CD8+ T cells provided co-stimulation and compensated for lower MHC class I expression. Altogether, our data indicate that triggering of both arms of the immune system is a promising approach applicable to the generation of a live attenuated HCMV vaccine.
开发一种有效的抗人巨细胞病毒（HCMV）疫苗具有极其重要的医学需求。一般认为，减毒活疫苗最能提供针对这种顽固病原体的保护性免疫。在此，我们提出一种针对HCMV疫苗的策略，旨在同时激活先天性和适应性免疫反应。发现一种表达NKG2D受体的宿主配体ULBP2的HCMV毒株易于受到自然杀伤（NK）细胞的控制，并保留了刺激HCMV特异性T细胞的能力。感染表达ULBP2的HCMV毒株导致MHC I类分子的细胞表面水平降低。虽然NKG2D配体的表达增加了NK细胞的细胞溶解活性，但NKG2D与CD8 + T细胞的结合提供了共刺激，并补偿了较低的MHC I类表达。总之，我们的数据表明，触发免疫系统的两个分支是一种有前景的方法，适用于减毒活HCMV疫苗的研发。
