engleski

Recombinant cytomegalovirus expressing NKG2D ligands: a model vaccine vector for infection and tumour treatment

Cytomegaloviruses (CMVs) encode numerous non- essential immunoevasive genes which can be deleted or replaced by any other gene without affecting viral growth or fitness in vitro. However, the deletion of viral immunoevasins attenuates the virus in vivo, thus enabling the generation of viruses with altered virulence. CMVs induce unique CD8 T cells response characterized by the accumulation of virus- specific CD8 T cells in the memory phase of infection making them an excellent candidate for the development of T cell-based vaccines. We have shown that murine CMV (MCMV) expressing ligand for activating receptor NKG2D, RAE-1γ, is highly attenuated in vivo but despite retains the capacity to induce strong adaptive immune response to viral and vectored antigens in infection and tumor model. Here we demonstrate that a recombinant MCMV expressing high affinity NKG2D ligand MULT-1 is dramatically attenuated in vivo by NK cells even stronger than RAE-1γMCMV, but still capable of inducing CD8 T cells response specific for the viral and vectored antigens. Similar to RAE-1γMCMV, in vitro studies have shown that MULT-1 expressing virus provides a strong costimulation of T cells apparently overcoming viral evasion of other costimulatory signals. Altogether, this study provides additional evidence that CMV expressing NKG2D ligands possesses characteristics which makes it a very promising candidate to be used as a vaccine vector.

recombinant cmv, vaccine, NKG2D, CD8 T cells

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