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Link, Ellen K.; Brandmüller, Christine; Suezer, Yasemin; Ameres, Stefanie; Volz, Asisa; Moosmann, Andreas; Sutter, Gerd; Lehmann, Michael H. (2017): A synthetic human cytomegalovirus pp65-IE1 fusion antigen efficiently induces and expands virus specific T cells. In: Vaccine, Vol. 35, Nr. 38: S. 5131-5139
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Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA. This recombinant MVA, MVA-syn65JE1, allowed for. the production of a stable similar to 120 kDa syn65_1E1 fusion protein upon tissue culture infection. MVA-syn65JE1 infected CD40-activated B cells activated and expanded pp65-and 1E1 -specific T cells derived from HCMV-seropositive donors to at least equal levels as control recombinant MVA expressing single genes for pp65 or IEl. Additionally, we show that MVA-syn65_1E1 induced HCMV pp65-and 1E1epitope specific T cells in H/A-A2.1-/HLA-DR1-transgenic H-2 class Hclass II -knockout mice. Thus, MVAsyn65_1E1 represents a promising vaccine candidate against HCMV and constitutes a basis for the generation of a multivalent vaccine targeting relevant pathogens in immunocompromised patients.