CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice

Summary

The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen‐presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T‐cell receptor complex a plethora of co‐stimulatory signals not only ensures a proper T‐cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The tumour necrosis factor receptor/ligand pair CD27/ CD70 gained a lot of attention because of its key role in regulating T‐cell activation, survival, differentiation and maintenance, especially in the course of viral infections and cancer. We sought to investigate the role of CD70 co‐stimulation for immune responses induced by the vaccine vector modified vaccinia virus Ankara–Bavarian Nordic ^® ( MVA‐ BN ^®). Short‐term blockade of CD70 diminished systemic CD8 T‐cell effector and memory responses in mice. The dependence on CD70 became even more apparent in the lungs of MHC class II‐deficient mice. Importantly, genetically encoded CD70 in MVA‐ BN ^® not only increased CD8 T‐cell responses in wild‐type mice but also substituted for CD4 T‐cell help. MHC class II‐deficient mice that were immunized with recombinant MVA‐ CD70 were fully protected against a lethal virus infection, whereas MVA‐ BN ^®‐immunized mice failed to control the virus. These data are in line with CD70 playing an important role for vaccine‐induced CD8 T‐cell responses and prove the potency of integrating co‐stimulatory molecules into the MVA‐ BN ^® backbone.