Gasteiger Georg, Kastenmuller Wolfgang, Ljapoci Ronny, Sutter Gerd, Drexler Ingo
GSF-Institute for Molecular Virology, Schneckenburgerstrasse 8, D-81675 Munich, Germany.
J Virol. 2007 Nov;81(21):11925-36. doi: 10.1128/JVI.00903-07. Epub 2007 Aug 15.
Recombinant vaccines based on modified vaccinia virus Ankara (MVA) have an excellent record concerning safety and immunogenicity and are currently being evaluated in numerous clinical studies for immunotherapy of infectious diseases and cancer. However, knowledge about the biological properties of target antigens to efficiently induce MVA vaccine-mediated immunity in vivo is sparse. Here, we examined distinct antigen presentation pathways and different antigen formulations contained in MVA vaccines for their capability to induce cytotoxic CD8(+) T-cell (CTL) responses. Strikingly, we found that CTL responses against MVA-produced antigens were dominated by cross-priming in vivo, despite the ability of the virus to efficiently infect professional antigen-presenting cells such as dendritic cells. Moreover, stable mature protein was preferred to preprocessed antigen as the substrate for cross-priming. Our data are essential for improved MVA vaccine design, as they demonstrate the need for optimal adjustment of the target antigen properties to the intrinsic requirements of the delivering vector system.
基于安卡拉痘苗病毒（MVA）的重组疫苗在安全性和免疫原性方面有着出色的记录，目前正在众多临床研究中接受评估，用于传染病和癌症的免疫治疗。然而，关于靶抗原在体内有效诱导MVA疫苗介导免疫的生物学特性的了解却很少。在此，我们研究了MVA疫苗中不同的抗原呈递途径和不同的抗原制剂诱导细胞毒性CD8(+) T细胞（CTL）反应的能力。令人惊讶的是，我们发现针对MVA产生抗原的CTL反应在体内主要由交叉呈递主导，尽管该病毒能够有效感染专职抗原呈递细胞，如树突状细胞。此外，稳定的成熟蛋白比预处理抗原更适合作为交叉呈递的底物。我们的数据对于改进MVA疫苗设计至关重要，因为它们表明需要根据递送载体系统的内在要求对靶抗原特性进行优化调整。
