A New In Vivo Model to Study Protective Immunity to Zika Virus Infection in Mice With Intact Type I Interferon Signaling

The association between recent Zika virus (ZIKV) infection and neurological complications, microcephaly in the fetus, and Guillain-Barré syndrome in adults underscores the necessity for a protective vaccine. Rational vaccine development requires an in-depth understanding of the mechanisms which could protect against infection with this virus. However, so far, such an analysis has been hampered by the absence of a suitable small animal model. Unlike the situation in humans, ZIKV only replicates effectively in the peripheral organs of mice, if type I IFN signaling is interrupted. As type I IFN also impacts the adaptive immune response, mice with such a defect are not optimal for a comprehensive immunological analysis. In this report, we show that even in wild-type (WT) mice i.c. infection with low doses of virus causes marked local virus replication and lethal encephalitis in naïve mice. Furthermore, peripheral infection of WT mice with low doses of virus induces a significant immune response, which provides long-lasting protection of WT mice from a fatal outcome of subsequent i.c. challenge. Therefore, combining peripheral priming with later i.c. challenge represents a new approach for studying the adaptive immune response to ZI...Continue Reading