title: Robust immunity to an auxotrophic Mycobacterium bovis BCG-VLP prime-boost HIV vaccine candidate in a nonhuman primate model.
abstract: We previously reported that a recombinant pantothenate auxotroph of Mycobacterium bovis BCG expressing human immunodeficiency virus type 1 (HIV-1) subtype C Gag (rBCGpan-Gag) efficiently primes the mouse immune system for a boost with a recombinant modified vaccinia virus Ankara (rMVA) vaccine. In this study, we further evaluated the immunogenicity of rBCGpan-Gag in a nonhuman primate model. Two groups of chacma baboons were primed or mock primed twice with either rBCGpan-Gag or a control BCG. Both groups were boosted with HIV-1 Pr55(gag) virus-like particles (Gag VLPs). The magnitude and breadth of HIV-specific cellular responses were measured using a gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay, and the cytokine profiles and memory phenotypes of T cells were evaluated by polychromatic flow cytometry. Gag-specific responses were detected in all animals after the second inoculation with rBCGpan-Gag. Boosting with Gag VLPs significantly increased the magnitude and breadth of the responses in the baboons that were primed with rBCGpan-Gag. These responses targeted an average of 12 Gag peptides per animal, compared to an average of 3 peptides per animal for the mock-primed controls. Robust responses of Gag-specific polyfunctional T cells capable of simultaneously producing IFN-γ, tumor necrosis alpha (TNF-α), and interleukin-2 (IL-2) were detected in the rBCGpan-Gag-primed animals. Gag-specific memory T cells were skewed toward a central memory phenotype in both CD4(+) and CD8(+) T cell populations. These data show that the rBCGpan-Gag prime and Gag VLP boost vaccine regimen is highly immunogenic, inducing a broad and polyfunctional central memory T cell response. This report further indicates the feasibility of developing a BCG-based HIV vaccine that is safe for childhood HIV immunization.
authors: Division of Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors: Gerald K
authors: GK
authors: Chege
authors: Wendy A
authors: WA
authors: Burgers
authors: Helen
authors: H
authors: Stutz
authors: Ann E
authors: AE
authors: Meyers
authors: Rosamund
authors: R
authors: Chapman
authors: Agano
authors: A
authors: Kiravu
authors: Rubina
authors: R
authors: Bunjun
authors: Enid G
authors: EG
authors: Shephard
authors: William R
authors: WR
authors: Jacobs
authors: Edward P
authors: EP
authors: Rybicki
authors: Anna-Lise
authors: AL
authors: Williamson
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D048549:Papio ursinus; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D014409:Tumor Necrosis Factor-alpha; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma