engleski

Vaccines and innate immunity: lessons from cytomegalovirus immunoevasion

Cytomegalovirus (CMV) establishes life-long infection of its host, ensuring continuous supply of effector memory CD8+ T cells. CMVs possess numerous immunoevasion genes able to modulate basically any part of immune response, including NK cell and CD8+ T cell response. It is well established that deletion of these viral inhibitors leads to virus attenuation in vivo.These features make CMV a very attractive CD8+ T cell vaccine vector candidate. Control of CMV infection is in great part dependent on NKG2D, an activating receptor when expressed on NK cells and co- stimulatory one when expressed on CD8+ T cells. We have constructed highly attenuated mouse CMV (MCMV) expressing NKG2D ligand RAE- 1γ inserted in place of its viral inhibitor (Slavuljica et al, 2010) and foreign CD8+ T cell epitope as well (Trsan et al, 2013). Such a recombinant vaccine- vector provided outstanding and long-lasting CD8+ T cell-mediated protection against challenge infections. Moreover, RAE-1γMCMV-vector circumvented MCMV interference of antigen presentation, improved antigen presentation to CD8+ T cells and potentiated memory CD8+ T cell response. Surprisingly, these immuno enhancing properties of RAE-1γ expressing MCMV vector were retained even in NKG2D deficient mice, pointing to additional NKG2D-independent immune function of RAE-1γ. In my talk, I will discuss the capacity of MCMV expressing RAE-1γ as a vaccine vector against other pathogens, as well as tumors.

vaccine vectors; NKG2D; CMV; CD8+ T cells; RAE-1γ

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