title: Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya.
abstract: We report the first trial of candidate malaria vaccine antigen FMP1, a 42kDa fragment from the C-terminus of merozoite surface protein-1 (MSP-1) from the 3D7 strain of Plasmodium falciparum, in an endemic area. Forty adult male and female residents of western Kenya were enrolled to receive 3 doses of either FMP1/AS02A or Imovax rabies vaccine by intra-deltoid injection on a 0, 1, 2 month schedule. Thirty-seven volunteers received all three immunizations and 38 completed the 12-month evaluation period. Slightly more recipients of the FMP1/AS02A vaccine experienced any instance of pain at 24 h post-immunization than in the Imovax group (95% versus 65%), but otherwise the two vaccines were equally safe and well-tolerated. Baseline antibody levels were high in both groups and were boosted in the FMP1/AS02A group. Longitudinal models revealed a highly significant difference between groups for both the average post-baseline antibody responses to MSP-1(42) (F1,335=13.16; P<0.001) and the Day 90 responses to MSP-1(42) (F1,335=16.69; P<0.001). The FMP1/AS02A vaccine is safe and immunogenic in adults and should progress to safety testing in children at greatest risk of malaria.
authors.affiliation: US Army Medical Research Unit and the Kenya Medical Research Institute, Nairobi, Kenya. jstoute@usuhs.mil
authors.forename: José A
authors.initials: JA
authors.lastname: Stoute
authors.forename: Joash
authors.initials: J
authors.lastname: Gombe
authors.forename: Mark R
authors.initials: MR
authors.lastname: Withers
authors.forename: Joram
authors.initials: J
authors.lastname: Siangla
authors.forename: Denise
authors.initials: D
authors.lastname: McKinney
authors.forename: Melanie
authors.initials: M
authors.lastname: Onyango
authors.forename: James F
authors.initials: JF
authors.lastname: Cummings
authors.forename: Jessica
authors.initials: J
authors.lastname: Milman
authors.forename: Kathryn
authors.initials: K
authors.lastname: Tucker
authors.forename: Lorraine
authors.initials: L
authors.lastname: Soisson
authors.forename: V Ann
authors.initials: VA
authors.lastname: Stewart
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lyon
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: Amanda
authors.initials: A
authors.lastname: Leach
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Holland
authors.forename: Carter L
authors.initials: CL
authors.lastname: Diggs
authors.forename: Janet
authors.initials: J
authors.lastname: Wittes
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007630:Kenya; D008050:Lipid A / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology; D012503:Saponins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D016896:Treatment Outcome
chemical_list: C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D004338:Drug Combinations; D008050:Lipid A; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D012503:Saponins