Natural IgG protects against early dissemination of vesicular stomatitis virus

Neonatal Fc receptor (FcRn) recycles immunoglobulin G, and inhibition of FcRn is used clinically for treatment of autoimmune diseases. In this work, using the vesicular stomatitis virus (VSV) mouse infection model system, we determined the role of FcRn during virus infection. While induction of neutralizing antibodies and long-term protection of these antibodies was hardly affected in FcRn deficient mice, FcRn deficiency limited the amount of natural IgG (VSV-specific) antibodies. Lack of natural antibodies (nAbs) limited early control of VSV in macrophages, accelerated propagation of virus in several organs, led to the spread of VSV to the neural tissue resulting in fatal outcomes. Adoptive transfer of natural IgG into FcRn deficient mice limited early propagation of VSV in FcRn deficient mice and enhanced survival of FcRn knockout mice. In line with this, vaccination of FcRn mice with very low dose of VSV prior to infection similarly prevented death after infection. In conclusion we determined the importance of nAbs during VSV infection. Lack of FcRn limited nAbs and thereby enhanced the susceptibility to virus infection. •FcRn deficiency minimally impacted induction and long-term protection of neutralizing antibodies against VSV.•Natural VSV-specific IgG antibodies are crucial for early viral control; reduced in FcRn-deficient animals.•Adoptive transfer of natural IgG into FcRn-deficient mice restricts early VSV propagation, enhancing survival.•Vaccination of FcRn-deficient mice prior to infection also prevented mortality after VSV infection.