title: Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1.
abstract: Virus diversity and escape from immune responses are the biggest challenges to the development of an effective vaccine against HIV-1. We hypothesized that T-cell vaccines targeting the most conserved regions of the HIV-1 proteome, which are common to most variants and bear fitness costs when mutated, will generate effectors that efficiently recognize and kill virus-infected cells early enough after transmission to potentially impact on HIV-1 replication and will do so more efficiently than whole protein-based T-cell vaccines. Here, we describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4(+) cells and inhibited HIV-1 replication by up to 5.79 log10. The virus inhibition was mediated by both Gag- and Pol- specific effector CD8(+) T cells targeting epitopes that are typically subdominant in natural infection. These results provide proof of concept for using a vaccine to target T cells at conserved epitopes, showing that these T cells can control HIV-1 replication in vitro.
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Borthwick
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK.
authors.forename: Tina
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ondondo
authors.affiliation: IAVI Human Immunology Laboratory, Imperial College, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Hayes
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Annie
authors.initials: A
authors.lastname: Rose
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Umar
authors.initials: U
authors.lastname: Ebrahimsa
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Emma-Jo
authors.initials: EJ
authors.lastname: Hayton
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK; Current address: Institut Pasteur du Laos, Vientiane, Laos People's Democratic Republic.
authors.forename: Antony
authors.initials: A
authors.lastname: Black
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Bridgeman
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK; Current address: Medical Microbiology and Immunology, Li Ka Shing Institute of Virology, 6-096 Katz Centre for Health Research, Edmonton, Alberta, Canada.
authors.forename: Maximillian
authors.initials: M
authors.lastname: Rosario
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK; Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK; Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Adrian Vs
authors.initials: AV
authors.lastname: Hill
authors.affiliation: Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Berrie
authors.affiliation: Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Moyle
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.affiliation: IAVI Human Immunology Laboratory, Imperial College, London, UK.
authors.forename: Josephine
authors.initials: J
authors.lastname: Cox
authors.affiliation: Okairos, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Colloca
authors.affiliation: Okairos, Rome, Italy; CEINGE, Naples, Italy; Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.affiliation: IAVI Human Immunology Laboratory, Imperial College, London, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
authors.affiliation: The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, UK; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK; Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, University of Oxford, Churchill Hospital, Oxford, UK; Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, UK. Electronic address: tomas.hanke@ndm.ox.ac.uk.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000276:immunology; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus