title: Heterologous Immunity between Adenoviruses and Hepatitis C Virus: A New Paradigm in HCV Immunity and Vaccines.
abstract: Adenoviruses (Ad) are commonly used as vectors for gene therapy and/or vaccine delivery. Recombinant Ad vectors are being tested as vaccines for many pathogens. We have made a surprising observation that peptides derived from various hepatitis C virus (HCV) antigens contain extensive regions of homology with multiple adenovirus proteins, and conclusively demonstrate that adenovirus vector can induce robust, heterologous cellular and humoral immune responses against multiple HCV antigens. Intriguingly, the induction of this cross-reactive immunity leads to significant reduction of viral loads in a recombinant vaccinia-HCV virus infected mouse model, supporting their role in antiviral immunity against HCV. Healthy human subjects with Ad-specific pre-existing immunity demonstrated cross-reactive cellular and humoral immune responses against multiple HCV antigens. These findings reveal the potential of a previously uncharacterized property of natural human adenovirus infection to dictate, modulate and/or alter the course of HCV infection upon exposure. This intrinsic property of adenovirus vectors to cross-prime HCV immunity can also be exploited to develop a prophylactic and/or therapeutic vaccine against HCV.
authors.affiliation: Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Shakti
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.|Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Satish
authors.initials: S
authors.lastname: Vedi
authors.affiliation: Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Subodh Kumar
authors.initials: SK
authors.lastname: Samrat
authors.affiliation: Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Babita
authors.initials: B
authors.lastname: Agrawal
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry; D049109:Cell Proliferation; D045142:Cross-Priming; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000276:immunology; D018936:Hepatitis C Antigens / Q000276:immunology; D006801:Humans; D064789:Immunity, Heterologous; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D014614:Vaccines, Synthetic / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D010455:Peptides; D014614:Vaccines, Synthetic; D014761:Viral Hepatitis Vaccines; D007371:Interferon-gamma