Recombinant rabies virus expressing IFN alpha 1 enhanced immune responses resulting in its attenuation and stronger immunogenicity

Several studies have shown that type 1 interferons (IFNs) exert multiple biological effects on both innate and adaptive immune responses. Here, we investigated the pathogenicity and immunogenicity of recombinant rabies virus (RABV) expressing canine interferon alpha 1 (rHEP-CaIFN alpha 1). It was shown that Kun Ming (KM) mice that received a single intramuscular immunization with rHEP-CaIFN alpha 1 had an earlier increase and a higher level of virus-neutralizing antibody titers compared with immunization of the parent HEP-Flury. A challenge experiment further confirmed that more mice that were immunized with rHEP-CaIFN alpha 1 survived compared with mice immunized with the parent virus. Quantitative real-time PCR indicated that rHEP-CaIFN alpha 1 induced a stronger innate immune response, especially the type 1 IFN response. Flow cytometry was conducted to show that rHEP-CaIFN alpha 1 recruited more activated B cells in lymph nodes and CD8 T cells in the peripheral blood, which is beneficial to achieve virus clearance in the early infective stage.