title: Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara.
abstract: Malaria is a major global health problem for which an effective vaccine is required urgently. Prime-boost vaccination regimes involving plasmid DNA and recombinant modified vaccinia virus Ankara-encoding liver-stage malaria antigens have been shown to be powerfully immunogenic for T cells and capable of inducing partial protection against experimental malaria challenge in humans, manifested as a delay in time to patent parasitemia. Here, we report that substitution of plasmid DNA as the priming vector with a specific attenuated recombinant fowlpox virus, FP9, vaccine in such prime-boost regimes can elicit complete sterile protection that can last for 20 months. Protection at 20 months was associated with persisting memory but not effector T cell responses. The protective efficacy of various immunization regimes correlated with the magnitude of induced immune responses, supporting the strategy of maximizing durable T cell immunogenicity to develop more effective liver-stage vaccines against Plasmodium falciparum malaria.
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Old Road, Oxford OX3 7LJ, UK.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Webster
authors.forename: Susanna
authors.initials: S
authors.lastname: Dunachie
authors.forename: Jenni M
authors.initials: JM
authors.lastname: Vuola
authors.forename: Tamara
authors.initials: T
authors.lastname: Berthoud
authors.forename: Sheila
authors.initials: S
authors.lastname: Keating
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Laidlaw
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: McConkey
authors.forename: Ian
authors.initials: I
authors.lastname: Poulton
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Rikke F
authors.initials: RF
authors.lastname: Andersen
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.forename: Geoff
authors.initials: G
authors.lastname: Butcher
authors.forename: Robert
authors.initials: R
authors.lastname: Sinden
authors.forename: Michael A
authors.initials: MA
authors.lastname: Skinner
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000328:Adult; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005587:Fowlpox virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods*; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma