title: Synergistic effect of combined HIV/HCV immunogens: a combined HIV-1/HCV candidate vaccine induces a higher level of CD8+ T cell-immune responses in HLA-A2.1 mice.
abstract: Dual infections with HIV-1 and Hepatitis C virus (HCV) may proceed in concert to cause severe disease. HIV positive individuals that become infected with HCV advance more rapidly to AIDS than those that are infected with HIV-1 alone. In this study, HLA-A2.1 mice were immunized with a combination vaccine including HIV and HCV immunogens (polycistronic DNA + proteins) or vaccine containing either HIV or HCV immunogens. Mice immunized with the combined HIV/HCV regimen had similar antibody titers as the group receiving either the HIV-1 or HCV only regimen. Proliferative immune responses showed that mice receiving the combined HIV/HCV vaccine exhibited a three fold higher stimulation index (SI) to gp120 than mice immunized with the vaccine containing HIV alone. To determine whether our vaccine strategy induced Th1 or Th2 immune responses, IFN-gamma and IL-4/IL-5 were measured. The combined HIV/HCV vaccine induced a higher level of Th1 responses to HIV-1 gag protein compared with the other groups, as measured by IFN-gamma production. Interestingly, detection of IFN-gamma by ELISPOT assay demonstrated that the combined HIV/HCV vaccine group had increased numbers of spot forming cells (SFC) to HIV-gp120 peptides when compared to that of the HIV-1 only vaccine group. The combined HIV/HCV vaccine group also showed an increase in SFC to HCV-core peptides in comparison with the group receiving the HCV only vaccine. Intracellular IFN-gamma staining confirmed the ELISPOT results and demonstrated that the combined HIV/HCV group had significantly higher percentages of HIV and HCV-specific CD8+ T cells in comparison to the groups receiving the HIV or HCV vaccines. These results suggest a new approach to maximize vaccine efficacy against HIV and HCV.
authors.affiliation: Infectious Disease and Vaccine Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Azizi
authors.forename: Masoud
authors.initials: M
authors.lastname: Ghorbani
authors.forename: Catalina
authors.initials: C
authors.lastname: Soare
authors.forename: Majid
authors.initials: M
authors.lastname: Mojibian
authors.forename: Francisco
authors.initials: F
authors.lastname: Diaz-Mitoma
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018929:Cell Culture Techniques; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D006678:HIV / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D018418:Th2 Cells / Q000276:immunology / Q000821:virology; D017778:Vaccines, Combined / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014761:Viral Hepatitis Vaccines
chemical_list: D016915:AIDS Vaccines; D015683:Gene Products, gag; D015789:HLA-A2 Antigen; D017778:Vaccines, Combined; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D007371:Interferon-gamma