title: A genetically engineered live-attenuated simian-human immunodeficiency virus that co-expresses the RANTES gene improves the magnitude of cellular immunity in rhesus macaques.
abstract: Regulated-on-activation-normal-T-cell-expressed-and-secreted (RANTES), a CC-chemokine, enhances antigen-specific T helper (Th) type-1 responses against HIV-1. To evaluate the adjuvant effects of RANTES against HIV vaccine candidate in SHIV-macaque models, we genetically engineered a live-attenuated SHIV to express the RANTES gene (SHIV-RANTES) and characterized the virus's properties in vivo. After the vaccination, the plasma viral loads were same in the SHIV-RANTES-inoculated monkeys and the parental nef-deleted SHIV (SHIV-NI)-inoculated monkeys. SHIV-RANTES provided some immunity in monkeys by remarkably increasing the antigen-specific CD4+ Th cell-proliferative response and by inducing an antigen-specific IFN-gamma ELISpot response. The magnitude of the immunity in SHIV-RANTES-immunized animals, however, failed to afford greater protection against a heterologous pathogenic SHIV (SHIV-C2/1) challenge compared to control SHIV-NI-immunized animals. SHIV-RANTES immunized monkeys, elicited robust cellular CD4+ Th responses and IFN-gamma ELISpot responses after SHIV-C2/1 challenge. These findings suggest that the chemokine RANTES can augment vaccine-elicited, HIV-specific CD4+ T cell responses.
authors.affiliation: Department of Veterinary Microbiology, University of Miyazaki, Miyazaki 889-2192, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Inaba
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kaneyasu
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ibuki
authors.forename: Ai
authors.initials: A
authors.lastname: Himeno
authors.forename: Masashi
authors.initials: M
authors.lastname: Okoba
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Goto
authors.forename: Masanori
authors.initials: M
authors.lastname: Hayami
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Haga
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D000276:Adjuvants, Immunologic; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008253:Macaca mulatta; D008297:Male; D016865:Reassortant Viruses / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D014611:Vaccination; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D018946:Chemokine CCL5; D015488:HIV Antigens; D007371:Interferon-gamma