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Expression of NKG2D ligand by cytomegalovirus enhances its vaccine vector capacity

Although vaccination proved to be successful method against various pathogens, efficient vaccine for a significant number of diseases is still not available. Therefore, new vaccine strategies are required. Live attenuated CMVs are attractive candidates as vaccine vectors due to the potent immune response they trigger. CMVs developed numerous strategies to avoid immune control of the host, especially the one mediated by the NKG2D receptor, expressed on the cells of both innate and adaptive immunity. Our laboratory has previously shown that recombinant murine CMV (MCMV) expressing NKG2D ligand RAE-1γ induces strong virus-specific CD8+ T cell response in spite of dramatic attenuation in vivo. Here we present the ability of such recombinant virus to serve as a CD8+ T cells based vaccine. On the backbone of MCMV expressing RAE-1 we have constructed recombinant viruses bearing immunodominant CD8+ T cell epitopes such as listeriolysin of Listeria monocytogenes or SIINFEKL peptide derived from ovalbumin. Our results demonstrated that herpesviruses engineered to express NKG2D ligand in addition to a foreign CD8+ T cell epitope dramatically improved efficacy and longevity of the protective CD8+ T cell response, suggesting a new powerful approach for designing immunologically attenuated viruses as vaccine vectors.

Murine cytomegalovirus; NKG2D; CMV vaccine vector; CD8 T cell vaccine

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