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.
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.
Genton
Blaise
B
Papua New Guinea Institute of Medical Research, Maprik, Papua New Guinea. Blaise.genton@hospvd.ch
Betuela
Inoni
I
Felger
Ingrid
I
Al-Yaman
Fadwa
F
Anders
Robin F
RF
Saul
Allan
A
Rare
Lawrence
L
Baisor
Moses
M
Lorry
Kerry
K
Brown
Graham V
GV
Pye
David
D
Irving
David O
DO
Smith
Thomas A
TA
Beck
Hans-Peter
HP
Alpers
Michael P
MP
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*
D017780:Malaria Vaccines; D014614:Vaccines, Synthetic