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Work package 3

Novel cytomegalovirus-based vaccines and vectors

VaccinationInfectious diseases have a tremendous impact on public health. However, for some pathogens there are still no available vaccines, whereas for others the current vaccine approaches are not sufficiently effective. The aim of this WP is to characterize an innovative vaccine vector(s) based on attenuated CMVs expressing cellular ligand for an activating innate immune receptor, NKG2D. The idea stems from our original finding which suggests that a recombinant herpesvirus expressing the NKG2D ligand has the outstanding property to augment the effectiveness and longevity of the specific CD8 T cell response (Slavuljica et al., J Clin Invest, 2010; Trsan et al, Proc Natl Acad Sci USA, 2013.).

CMVs are excellent inducers of the CD8 T cell response, in spite of having numerous immunoevasion strategies aimed at compromising antigen presentation by MHC class I molecules (Reddehase, Nat Rev Immunol, 2002). Preferentially, CMVs induce the effector arm of memory CD8 T cells (Lemmermann et al., Vir Res, 2011). In addition, CMV activates memory T-cell biased toward mucosal tissue distribution, which might be particularly relevant to the therapeutic control of cancer and control of pathogens directly at their sites of entry. The suitability of CMV as a vaccine vector was emphasized in a recent study by Hansen and colleagues (Hansen et al., Science, 2013). Based on the preliminary data, we are performing studies aimed at characterizing novel CMV-based vectors against several microbial pathogens and tumors.