title: Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans.
abstract: In animals, effective immune responses against malignancies and against several infectious pathogens, including malaria, are mediated by T cells. Here we show that a heterologous prime-boost vaccination regime of DNA either intramuscularly or epidermally, followed by intradermal recombinant modified vaccinia virus Ankara (MVA), induces high frequencies of interferon (IFN)-gamma-secreting, antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen, thrombospondin-related adhesion protein (TRAP). These responses are five- to tenfold higher than the T-cell responses induced by the DNA vaccine or recombinant MVA vaccine alone, and produce partial protection manifest as delayed parasitemia after sporozoite challenge with a different strain of Plasmodium falciparum. Such heterologous prime-boost immunization approaches may provide a basis for preventative and therapeutic vaccination in humans.
authors.affiliation: Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: McConkey
authors.forename: William H H
authors.initials: WH
authors.lastname: Reece
authors.forename: Vasee S
authors.initials: VS
authors.lastname: Moorthy
authors.forename: Daniel
authors.initials: D
authors.lastname: Webster
authors.forename: Susanna
authors.initials: S
authors.lastname: Dunachie
authors.forename: Geoff
authors.initials: G
authors.lastname: Butcher
authors.forename: Jenni M
authors.initials: JM
authors.lastname: Vuola
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Blanchard
authors.forename: Philip
authors.initials: P
authors.lastname: Gothard
authors.forename: Kate
authors.initials: K
authors.lastname: Watkins
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hannan
authors.forename: Simone
authors.initials: S
authors.lastname: Everaere
authors.forename: Karen
authors.initials: K
authors.lastname: Brown
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: James
authors.initials: J
authors.lastname: Cummings
authors.forename: Jackie
authors.initials: J
authors.lastname: Williams
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
authors.forename: Ansar
authors.initials: A
authors.lastname: Pathan
authors.forename: Katie
authors.initials: K
authors.lastname: Flanagan
authors.forename: Nirmalan
authors.initials: N
authors.lastname: Arulanantham
authors.forename: Mark T M
authors.initials: MT
authors.lastname: Roberts
authors.forename: Michael
authors.initials: M
authors.lastname: Roy
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Smith
authors.forename: Joerg
authors.initials: J
authors.lastname: Schneider
authors.forename: Tim
authors.initials: T
authors.lastname: Peto
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control / Q000628:therapy; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D010957:Plasmids; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma