Recombinant lymphocytic choriomeningitis virus-based vaccine vector protects type I interferon receptor deficient mice from viral challenge

Michal Krolik; Lucia Csepregi; Fabienne Hartmann; Céline Engetschwiler; Lukas Flatz

doi:10.1016/j.vaccine.2021.01.047

Recombinant lymphocytic choriomeningitis virus-based vaccine vector protects type I interferon receptor deficient mice from viral challenge

Vaccine. 2021 Feb 22;39(8):1257-1264. doi: 10.1016/j.vaccine.2021.01.047. Epub 2021 Jan 29.

Authors

Michal Krolik¹, Lucia Csepregi¹, Fabienne Hartmann¹, Céline Engetschwiler¹, Lukas Flatz²

Affiliations

¹ Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland.
² Institute of Immunobiology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland; Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland; Department of Oncology and Hematology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland; Department of Dermatology, Kantonsspital St.Gallen, Rorschacher Strasse 95, 9007 St.Gallen, Switzerland. Electronic address: [email protected].

PMID: 33518468
DOI: 10.1016/j.vaccine.2021.01.047

Abstract

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 CD8⁺ 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.

Keywords: Antiviral immunity; CD8(+) T cells; IFNAR; Innate immunity; LCMV; Viral vaccine vectors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD8-Positive T-Lymphocytes
Lymphocytic choriomeningitis virus*
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptor, Interferon alpha-beta* / genetics
Vaccines, Synthetic / genetics
Viral Vaccines*

Substances

Vaccines, Synthetic
Viral Vaccines
Receptor, Interferon alpha-beta