Recombinant rabies virus expressing IFNα1 enhanced immune responses resulting in its attenuation and stronger immunogenicity

Virology. 2014 Nov:468-470:621-630. doi: 10.1016/j.virol.2014.09.010. Epub 2014 Oct 11.

Abstract

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 α1 (rHEP-CaIFNα1). It was shown that Kun Ming (KM) mice that received a single intramuscular immunization with rHEP-CaIFNα1 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-CaIFNα1 survived compared with mice immunized with the parent virus. Quantitative real-time PCR indicated that rHEP-CaIFNα1 induced a stronger innate immune response, especially the type 1 IFN response. Flow cytometry was conducted to show that rHEP-CaIFNα1 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.

Keywords: Interferon; Rabies virus; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes
  • Cricetinae
  • Dogs
  • Gene Expression Regulation, Viral / immunology*
  • Genetic Engineering*
  • Immunity, Innate
  • Interferon-alpha / genetics
  • Interferon-alpha / metabolism*
  • Mice
  • RNA, Messenger
  • RNA, Viral
  • Rabies / prevention & control
  • Rabies / virology
  • Rabies Vaccines / immunology*
  • Rabies virus / genetics*
  • Rabies virus / immunology
  • Rabies virus / pathogenicity*
  • T-Lymphocytes
  • Vaccines, Attenuated
  • Virus Cultivation
  • Virus Replication

Substances

  • Interferon-alpha
  • RNA, Messenger
  • RNA, Viral
  • Rabies Vaccines
  • Vaccines, Attenuated