title: A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea.
abstract: The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic types.
authors.affiliation: Papua New Guinea Institute of Medical Research, Maprik, Papua New Guinea. Blaise.genton@hospvd.ch
authors.forename: Blaise
authors.initials: B
authors.lastname: Genton
authors.forename: Inoni
authors.initials: I
authors.lastname: Betuela
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
authors.forename: Fadwa
authors.initials: F
authors.lastname: Al-Yaman
authors.forename: Robin F
authors.initials: RF
authors.lastname: Anders
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rare
authors.forename: Moses
authors.initials: M
authors.lastname: Baisor
authors.forename: Kerry
authors.initials: K
authors.lastname: Lorry
authors.forename: Graham V
authors.initials: GV
authors.lastname: Brown
authors.forename: David
authors.initials: D
authors.lastname: Pye
authors.forename: David O
authors.initials: DO
authors.lastname: Irving
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Smith
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Beck
authors.forename: Michael P
authors.initials: MP
authors.lastname: Alpers
mesh_terms: D000818:Animals; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000517:prevention & control*; D010219:Papua New Guinea / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D017780:Malaria Vaccines; D014614:Vaccines, Synthetic