title: A human immunodeficiency virus 1 (HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans.
abstract: The immunogenicities of candidate DNA- and modified vaccinia virus Ankara (MVA)-vectored human immunodeficiency virus (HIV) vaccines were evaluated on their own and in a prime-boost regimen in phase I clinical trials in healthy uninfected individuals in the United Kingdom. Given the current lack of approaches capable of inducing broad HIV-neutralizing antibodies, the pTHr.HIVA DNA and MVA.HIVA vaccines focus solely on the induction of cell-mediated immunity. The vaccines expressed a common immunogen, HIVA, which consists of consensus HIV-1 clade A Gag p24/p17 proteins fused to a string of clade A-derived epitopes recognized by cytotoxic T lymphocytes (CTLs). Volunteers' fresh peripheral blood mononuclear cells were tested for HIV-specific responses in a validated gamma interferon enzyme-linked immunospot (ELISPOT) assay using four overlapping peptide pools across the Gag domain and three pools of known CTL epitopes present in all of the HIVA protein. Both the DNA and the MVA vaccines alone and in a DNA prime-MVA boost combination were safe and induced HIV-specific responses in 14 out of 18, seven out of eight and eight out of nine volunteers, respectively. These results are very encouraging and justify further vaccine development.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Matilu
authors.initials: M
authors.lastname: Mwau
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Inese
authors.initials: I
authors.lastname: Cebere
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Sutton
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Chikoti
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Winstone
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Edmund G-T
authors.initials: EG
authors.lastname: Wee
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Tara
authors.initials: T
authors.lastname: Beattie
authors.affiliation: University of St Andrews, School of Biology, St Andrews, UK.
authors.forename: Yun-Hsiang
authors.initials: YH
authors.lastname: Chen
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
authors.affiliation: Nuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.affiliation: International AIDS Vaccine Initiative, 110 William Street, New York, NY 10038, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Mary
authors.initials: M
authors.lastname: Brooks
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Sandip
authors.initials: S
authors.lastname: Patel
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Roberts
authors.affiliation: Nuffield Department of Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Conlon
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
authors.affiliation: Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya.
authors.forename: Job J
authors.initials: JJ
authors.lastname: Bwayo
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D005260:Female; D015683:Gene Products, gag; D015483:HIV Antibodies / Q000096:biosynthesis; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D012449:Safety; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D015683:Gene Products, gag; D015483:HIV Antibodies; D015488:HIV Antigens; D016655:HIV Core Protein p24; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1