title: Increased detection of proliferating, polyfunctional, HIV-1-specific T cells in DNA-modified vaccinia virus Ankara-vaccinated human volunteers by cultured IFN-gamma ELISPOT assay.
abstract: Induction of a long-term immunological memory, which can expand and defend the host upon pathogen encounter, is the "holy grail" of vaccinology. Here, using a sensitive cultured IFN-gamma ELISPOT assay, we show that 50% (15 out of 30) of healthy, HIV-1/2-uninfected volunteers who received pTHr.HIVA DNA prime-modified vaccinia virus Ankara. HIVA boost vaccine regimen 1 to 3 1/2 years ago had detectable HIV-1-specific T-cell responses. These T cells, predominantly of the CD4(+) subtype, could proliferate and produce multiple cytokines in response to in vitro peptide stimulation. Peptide mapping studies showed that the vaccine-induced CD4(+) T cells were mostly directed toward epitopes targeted in HIV-1-infected individuals. In addition, we used the same assay to re-evaluate 51 volunteers from past vaccine trial IAVI-006 and corrected the previously reported 10% of vaccine responders to 50%. Thus, we confirmed that cultured assays are a valuable tool for studying T-cell memory. These results are discussed in the context of the current state-of-affairs of the HIV-1 vaccine field.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Winstone
authors.forename: Ana
authors.initials: A
authors.lastname: Guimarães-Walker
authors.forename: Joanna
authors.initials: J
authors.lastname: Roberts
authors.forename: Denise
authors.initials: D
authors.lastname: Brown
authors.forename: Vanessa
authors.initials: V
authors.lastname: Loach
authors.forename: Nilu
authors.initials: N
authors.lastname: Goonetilleke
authors.forename: Tomás
authors.initials: T
authors.lastname: Hanke
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015488:HIV Antigens; D010455:Peptides; D019444:Vaccines, DNA; C509463:pTHr.HIVA; D007371:Interferon-gamma