title: Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation.
abstract: Induction of antigen-specific CD8(+) T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8(+) T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/10(6) peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls. The frequency of monofunctional interferon-γ-producing CD8(+) T cells, but not antibodies, correlates with sterile protection and delay in time to patency (P(corrected)=0.005). Vaccine-induced CD8(+) T cells provide protection against human malaria, suggesting that a major limitation of previous vaccination approaches has been the insufficient magnitude of induced T cells.
authors.affiliation: 1] The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK [2].
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Ewer
authors.forename: Geraldine A
authors.initials: GA
authors.lastname: O'Hara
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Duncan
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Collins
authors.forename: Susanne H
authors.initials: SH
authors.lastname: Sheehy
authors.forename: Arturo
authors.initials: A
authors.lastname: Reyes-Sandoval
authors.forename: Anna L
authors.initials: AL
authors.lastname: Goodman
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Edwards
authors.forename: Sean C
authors.initials: SC
authors.lastname: Elias
authors.forename: Fenella D
authors.initials: FD
authors.lastname: Halstead
authors.forename: Rhea J
authors.initials: RJ
authors.lastname: Longley
authors.forename: Rosalind
authors.initials: R
authors.lastname: Rowland
authors.forename: Ian D
authors.initials: ID
authors.lastname: Poulton
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Draper
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blagborough
authors.forename: Eleanor
authors.initials: E
authors.lastname: Berrie
authors.forename: Sarah
authors.initials: S
authors.lastname: Moyle
authors.forename: Nicola
authors.initials: N
authors.lastname: Williams
authors.forename: Loredana
authors.initials: L
authors.lastname: Siani
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.forename: Stefano
authors.initials: S
authors.lastname: Colloca
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
authors.forename: Alison M
authors.initials: AM
authors.lastname: Lawrie
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cortese
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000261:Adenoviruses, Simian / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma