title: Improved vaccine protection against retrovirus infection after co-administration of adenoviral vectors encoding viral antigens and type I interferon subtypes.
abstract: BACKGROUND
  Type I interferons (IFNs) exhibit direct antiviral effects, but also distinct immunomodulatory properties. In this study, we analyzed type I IFN subtypes for their effect on prophylactic adenovirus-based anti-retroviral vaccination of mice against Friend retrovirus (FV) or HIV.
  
  
  RESULTS
  Mice were vaccinated with adenoviral vectors encoding FV Env and Gag proteins alone or in combination with vectors encoding IFNα1, IFNα2, IFNα4, IFNα5, IFNα6, IFNα9 or IFNβ. Only the co-administration of adenoviral vectors encoding IFNα2, IFNα4, IFNα6 and IFNα9 resulted in strongly improved immune protection of vaccinated mice from subsequent FV challenge infection with high control over FV-induced splenomegaly and reduced viral loads. The level of protection correlated with augmented virus-specific CD4(+) T cell responses and enhanced antibody titers. Similar results were obtained when mice were vaccinated against HIV with adenoviral vectors encoding HIV Env and Gag-Pol in combination with various type I IFN encoding vectors. Here mainly CD4(+) T cell responses were enhanced by IFNα subtypes.
  
  
  CONCLUSIONS
  Our results indicate that certain IFNα subtypes have the potential to improve the protective effect of adenovirus-based vaccines against retroviruses. This correlated with augmented virus-specific CD4(+) T cell and antibody responses. Thus, co-expression of select type I IFNs may be a valuable tool for the development of anti-retroviral vaccines.
authors.affiliation: Department of Molecular and Medical Virology, Institute of Microbiology and Hygiene, Ruhr-University Bochum, Germany. wibke.bayer@uni-due.de
authors.forename: Wibke
authors.initials: W
authors.lastname: Bayer
authors.forename: Ruth
authors.initials: R
authors.lastname: Lietz
authors.forename: Teona
authors.initials: T
authors.lastname: Ontikatze
authors.forename: Lena
authors.initials: L
authors.lastname: Johrden
authors.forename: Matthias
authors.initials: M
authors.lastname: Tenbusch
authors.forename: Ghulam
authors.initials: G
authors.lastname: Nabi
authors.forename: Simone
authors.initials: S
authors.lastname: Schimmer
authors.forename: Peter
authors.initials: P
authors.lastname: Groitl
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf
authors.forename: Cassandra M
authors.initials: CM
authors.lastname: Berry
authors.forename: Klaus
authors.initials: K
authors.lastname: Uberla
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Wildner
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005622:Friend murine leukemia virus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006678:HIV / Q000235:genetics / Q000276:immunology / Q000502:physiology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012192:Retroviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D007370:Interferon Type I; D014765:Viral Vaccines