title: Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates.
abstract: Protein vaccines, if rendered immunogenic, would facilitate vaccine development against HIV and other pathogens. We compared in nonhuman primates (NHPs) immune responses to HIV Gag p24 within 3G9 antibody to DEC205 ("DEC-HIV Gag p24"), an uptake receptor on dendritic cells, to nontargeted protein, with or without poly ICLC, a synthetic double stranded RNA, as adjuvant. Priming s.c. with 60 μg of both HIV Gag p24 vaccines elicited potent CD4(+) T cells secreting IL-2, IFN-γ, and TNF-α, which also proliferated. The responses increased with each of three immunizations and recognized multiple Gag peptides. DEC-HIV Gag p24 showed better cross-priming for CD8(+) T cells, whereas the avidity of anti-Gag antibodies was ∼10-fold higher with nontargeted Gag 24 protein. For both protein vaccines, poly ICLC was essential for T- and B-cell immunity. To determine whether adaptive responses could be further enhanced, animals were boosted with New York vaccinia virus (NYVAC)-HIV Gag/Pol/Nef. Gag-specific CD4(+) and CD8(+) T-cell responses increased markedly after priming with both protein vaccines and poly ICLC. These data reveal qualitative differences in antibody and T-cell responses to DEC-HIV Gag p24 and Gag p24 protein and show that prime boost with protein and adjuvant followed by NYVAC elicits potent cellular immunity.
authors.affiliation: Vaccine Research Center and Cellular Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Flynn
authors.forename: Kathrin
authors.initials: K
authors.lastname: Kastenmüller
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wille-Reece
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Munir
authors.initials: M
authors.lastname: Alam
authors.forename: Ross W
authors.initials: RW
authors.lastname: Lindsay
authors.forename: Andres M
authors.initials: AM
authors.lastname: Salazar
authors.forename: Beatriz
authors.initials: B
authors.lastname: Perdiguero
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Gomez
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
authors.forename: Chae G
authors.initials: CG
authors.lastname: Park
authors.forename: Christine
authors.initials: C
authors.lastname: Trumpfheller
authors.forename: Tibor
authors.initials: T
authors.lastname: Keler
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Robert
authors.initials: R
authors.lastname: Seder
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology* / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D012330:RNA, Double-Stranded / Q000276:immunology / Q000494:pharmacology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D012330:RNA, Double-Stranded