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Vaccination with a recombinant LCMV based vector expressing tumor-associated or viral antigens is a safe and versatile method to induce an immune response against tumors or viral infections. Here, we describe the generation of recombinant LCMV vectors in which the gene encoding the viral LCMV-GP was substituted with a gene of interest (vaccine antigen). This renders the vaccine vector propagation-incompetent while it preserves the property of eliciting a strong cytotoxic T cell response.