title: Safety, immunogenicity, and efficacy of prime-boost immunization with recombinant poxvirus FP9 and modified vaccinia virus Ankara encoding the full-length Plasmodium falciparum circumsporozoite protein.
abstract: Heterologous prime-boost immunization with DNA and various recombinant poxviruses encoding malaria antigens is capable of inducing strong cell-mediated immune responses and partial protection in human sporozoite challenges. Here we report a series of trials assessing recombinant fowlpox virus and modified vaccinia virus Ankara encoding the Plasmodium falciparum circumsporozoite protein in various prime-boost combinations, doses, and application routes. For the first time, these vaccines were administered intramuscularly and at doses of up to 5 x 10(8) PFU. Vaccines containing this antigen proved safe and induced modest immune responses but showed no evidence of efficacy in a sporozoite challenge.
authors.affiliation: Centre for Clinical Vaccinology & Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, United Kingdom. mwalther@mrc.gm
authors.forename: Michael
authors.initials: M
authors.lastname: Walther
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Thompson
authors.forename: Susanna
authors.initials: S
authors.lastname: Dunachie
authors.forename: Sheila
authors.initials: S
authors.lastname: Keating
authors.forename: Stephen
authors.initials: S
authors.lastname: Todryk
authors.forename: Tamara
authors.initials: T
authors.lastname: Berthoud
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Rikke F
authors.initials: RF
authors.lastname: Andersen
authors.forename: Anne
authors.initials: A
authors.lastname: Moore
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Ian
authors.initials: I
authors.lastname: Poulton
authors.forename: Filip
authors.initials: F
authors.lastname: Dubovsky
authors.forename: Eveline
authors.initials: E
authors.lastname: Tierney
authors.forename: Simon
authors.initials: S
authors.lastname: Correa
authors.forename: Angela
authors.initials: A
authors.lastname: Huntcooke
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Butcher
authors.forename: Jack
authors.initials: J
authors.lastname: Williams
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002986:Clinical Trials as Topic; D017261:Glycosylphosphatidylinositols / Q000502:physiology; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D018512:Parasitemia / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D011212:Poxviridae / Q000235:genetics; D015800:Protozoan Proteins / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D000913:Antibodies, Protozoan; D017261:Glycosylphosphatidylinositols; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; C081751:plasmanylinositol glycan; D007371:Interferon-gamma