title: Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara.
abstract: Immunization with irradiated sporozoites can protect against malaria infection and intensive efforts are aimed at reproducing this effect with subunit vaccines. A particular sequence of subunit immunization with pre-erythrocytic antigens of Plasmodium berghei, consisting of single dose priming with plasmid DNA followed by a single boost with a recombinant modified vaccinia virus Ankara (MVA) expressing the same antigen, induced unprecedented complete protection against P. berghei sporozoite challenge in two strains of mice. Protection was associated with very high levels of splenic peptide-specific interferon-gamma-secreting CD8+ T cells and was abrogated when the order of immunization was reversed. DNA priming followed by MVA boosting may provide a general immunization regime for induction of high levels of CD8+ T cells.
authors.affiliation: Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, UK. joerg.schneider@ndm.ox.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Schneider
authors.forename: S C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: T J
authors.initials: TJ
authors.lastname: Blanchard
authors.forename: T
authors.initials: T
authors.lastname: Hanke
authors.forename: K J
authors.initials: KJ
authors.lastname: Robson
authors.forename: C M
authors.initials: CM
authors.lastname: Hannan
authors.forename: M
authors.initials: M
authors.lastname: Becker
authors.forename: R
authors.initials: R
authors.lastname: Sinden
authors.forename: G L
authors.initials: GL
authors.lastname: Smith
authors.forename: A V
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002642:Chick Embryo; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control; D017780:Malaria Vaccines; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010957:Plasmids; D010962:Plasmodium berghei / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D019444:Vaccines, DNA; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D017780:Malaria Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma