Cross-priming of cytotoxic T cells dictates antigen requisites for modified vaccinia virus Ankara vector vaccines.
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.
Gasteiger
Georg
G
GSF-Institute for Molecular Virology, Schneckenburgerstrasse 8, D-81675 Munich, Germany.
Kastenmuller
Wolfgang
W
Ljapoci
Ronny
R
Sutter
Gerd
G
Drexler
Ingo
I
D000818:Animals; D017951:Antigen Presentation; D045142:Cross-Priming; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology; D005347:Fibroblasts / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry; D006801:Humans; D007107:Immune System / Q000821:virology; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D013602:T-Lymphocytes, Cytotoxic / Q000821:virology*; D014616:Vaccinia virus / Q000378:metabolism*; D014765:Viral Vaccines / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D014765:Viral Vaccines
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