title: Immunisation with recombinant modified vaccinia virus Ankara expressing HIV-1 gag in HIV-1-infected subjects stimulates broad functional CD4+ T cell responses.
abstract: Virus-specific CD4+ T cells with IL-2-secreting and/or proliferative capacity are detected readily in HIV-1-infected long-term nonprogressors and rarely in persons with untreated progressive infection. The contribution of these cells to viraemia control is uncertain, but this question might be addressed in clinical therapeutic vaccination studies. However, the quality of T helper responses induced by currently available HIV-1 vaccine candidates has not been explored in depth. We determined the effect of vaccination with modified vaccinia virus Ankara (MVA) expressing HIV-1 gag p24/p17 (MVA.HIVA) on HIV-1-specific CD4+ T cell responses in 16 chronically infected, highly active antiretroviral therapy (HAART)-treated subjects using CD8-depleted IFN-gamma ELISPOT assays, intracellular cytokine staining assays for IL-2 and IFN-gamma, and a CFSE-based proliferation assay. Gag-specific CD4+ T cell responses were significantly increased in magnitude and breadth after vaccination and targeted both known and new epitopes, several of which were also recognised by healthy HIV-uninfected volunteers immunised with the same vaccines. The frequencies of CD4+ T cells expressing IL-2 or IFN-gamma, alone or simultaneously, were also augmented. These findings indicate that functional virus-specific T helper cells can be boosted by vaccination in chronic HIV-1 infection. Further evaluation of their role in viraemia control is warranted.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: Beatrice O
authors.initials: BO
authors.lastname: Ondondo
authors.forename: Hongbing
authors.initials: H
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Kati
authors.initials: K
authors.lastname: di Gleria
authors.forename: Annie
authors.initials: A
authors.lastname: Suttill
authors.forename: Christopher
authors.initials: C
authors.lastname: Conlon
authors.forename: Denise
authors.initials: D
authors.lastname: Brown
authors.forename: Patricia
authors.initials: P
authors.lastname: Williams
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.forename: Tomás
authors.initials: T
authors.lastname: Hanke
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D007376:Interleukin-2; D010446:Peptide Fragments; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C473991:p17 gag peptide, human immunodeficiency virus; D007371:Interferon-gamma