A genetically engineered live-attenuated simian–human immunodeficiency virus that co-expresses the RANTES gene improves the magnitude of cellular immunity in rhesus macaques

• Published in: Virology (New York, N.Y.) Vol. 361; no. 1; pp. 68 - 79
• Main Authors: Shimizu, Yuya, Inaba, Katsuhisa, Kaneyasu, Kentaro, Ibuki, Kentaro, Himeno, Ai, Okoba, Masashi, Goto, Yoshitaka, Hayami, Masanori, Miura, Tomoyuki, Haga, Takeshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.04.2007
• Subjects: Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - virology; Adjuvant; Adjuvants, Immunologic; Animals; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; Chemokine; Chemokine CCL5 - genetics; Chemokine CCL5 - immunology; Chemokine CCL5 - metabolism; HIV Antigens - immunology; HIV-1; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus 1; Infectious Disease; Interferon-gamma - biosynthesis; Macaca mulatta; Male; RANTES; Reassortant Viruses - genetics; Reassortant Viruses - immunology; Reassortant Viruses - metabolism; SHIV; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - immunology; Simian/human immunodeficiency virus; SIV; T-Cell Antigen Receptor Specificity; Vaccination; Vaccine; Viral Load; HIV-1; Chemokine; SIV; SHIV; RANTES; Adjuvant; Vaccine
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.10.050

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-γ 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-γ ELISpot responses after SHIV-C2/1 challenge. These findings suggest that the chemokine RANTES can augment vaccine-elicited, HIV-specific CD4+ T cell responses.