title: Clinical experience with plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency virus type 1 clade A vaccine focusing on T-cell induction.
abstract: Candidate human immunodeficiency virus type 1 (HIV-1) vaccines focusing on T-cell induction, constructed as pTHr.HIVA DNA and modified vaccinia virus Ankara (MVA).HIVA, were delivered in a heterologous prime-boost regimen. The vaccines were tested in several hundred healthy or HIV-1-infected volunteers in Europe and Africa. Whilst larger trials of hundreds of volunteers suggested induction of HIV-1-specific T-cell responses in <15 % of healthy vaccinees, a series of small, rapid trials in 12-24 volunteers at a time with a more in-depth analysis of vaccine-elicited T-cell responses proved to be highly informative and provided more encouraging results. These trials demonstrated that the pTHr.HIVA vaccine alone primed consistently weak and mainly CD4(+), but also CD8(+) T-cell responses, and the MVA.HIVA vaccine delivered a consistent boost to both CD4(+) and CD8(+) T cells, which was particularly strong in HIV-1-infected patients. Thus, whilst the search is on for ways to enhance T-cell priming, MVA is a useful boosting vector for human subunit genetic vaccines.
authors.affiliation: Weatherall Institute of Molecular Medicine, MRC Human Immunology Unit, University of Oxford, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
authors.affiliation: Weatherall Institute of Molecular Medicine, MRC Human Immunology Unit, University of Oxford, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.affiliation: Weatherall Institute of Molecular Medicine, MRC Human Immunology Unit, University of Oxford, The John Radcliffe, Oxford OX3 9DS, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Dorrell
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology; D006801:Humans; D010957:Plasmids / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA