Recombinant Lymphocytic Choriomeningitis Virus-Based Vaccine Vector Protects Type I Interferon Receptor Deficient Mice From Viral Challenge

Reverse genetically engineered recombinant lymphocytic choriomeningitis virus (rLCMV) is a novel vaccine vector platform. Here, we investigate the safety and efficacy of rLCMV in mice lacking a functional type I interferon system with high susceptibility to viral infections. Propagation-deficient rLCMV vector expressing ovalbumin as a model antigen is cleared from type I interferon receptor-deficient mice (Ifnar(-/-)) within seven days post vaccination. In Ifnar(-/-) , induction of vaccine antigen specific T cells is delayed compared to wild type animals. However, immunization of Ifnar(-/-) results in potent memory formation and generates multifunctional cytotoxic CDR+ T cells. Most importantly, Ifnar(-/-) vaccinated with rLCMV are protected from a challenge with the aggressive LCMV Clone 13. Our data provide evidence for an excellent safety profile with maintained efficacy in immunocompromised animals. (C) 2021 Elsevier Ltd. All rights reserved.