title: Enhanced Immune Responses against HIV-1 with Adenovector (Gag and Tat) Prime/Protein Boost Regimen and GM-CSF Injection.
abstract: Vaccines against the HIV-1 virus offers the best hope for eliminating HIV-associated mortality. Recombinant adenovector type 5 (rAd5) vaccine is a potential candidate for preventive vaccine strategies. In this study, we evaluated the rAd5 prime/protein boost strategy in a murine model. We used rAd5 harboring single HIV-1 genes. These genes, including gag (p24) and exon1 of tat, were amplified from HIV-1 (clade A) RNA using nested PCR. Recombinant vectors were constructed, purified and then injected at 1012 viral particles into four groups, each comprising five mice. The groups were each assigned to receive one of rAd5 prime/protein boost Gag, Tat with and without recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), and rAd5 with and without genes. The humoral responses were evaluated using ELISA and cellular immune responses checked by cell proliferation and ELISpot assays (IL-2, IL-4 and IFN-γ). It was shown that compared with the rAd5 injection alone, the rAd5 prime/protein boost plan increased cellular immunity (p= 0.009) as well as humoral immunity (p= 0.009). Moreover, rGM-CSF as an adjuvant enhanced cell-mediated immunity and increased IL-4 expression (p=0.032). The results revealed that the simultaneous use of multiple antigens and heterologous prime/boost strategy can enhance both humoral and cellular immune systems. Moreover, subcutaneous injection of rGM-CSF increases IL-4 production and shifts the immune pattern to Th2. These strategies can potentially be used to develop an efficient HIV-1 vaccine.
authors.affiliation: Department of Immunology, Faculty of Medicine, Tarbiat Modares University of Medical Sciences, Tehran, Iran.
authors.forename: Negin
authors.initials: N
authors.lastname: Hosseini Rouzbahani
authors.affiliation: Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Bayanolhagh
authors.affiliation: Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Gholami
authors.affiliation: Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Esmaeilzadeh
authors.affiliation: Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Bayat Jozani
authors.affiliation: Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Minoo
authors.initials: M
authors.lastname: Mohraz
authors.affiliation: Department of Immunology, Faculty of Medicine, Tarbiat Modares University of Medical Sciences, Tehran, Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Pourfathollah
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae; D000818:Animals; D016207:Cytokines / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D014161:Transduction, Genetic; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D054301:gag Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Adenovirus; HIV vaccine; Multiple antigen; Prime-boost; rGM-CSF