title: Strain-specific humoral response to a polymorphic malaria vaccine.
abstract: The 3D7 form of the merozoite surface protein 2 (MSP2) of Plasmodium falciparum was one of three subunits of the malaria vaccine Combination B that were tested in a phase I/IIb double-blind randomized placebo-controlled trial, which was undertaken with 120 Papua New Guinean children of 5 to 9 years of age. Because only one variant of the highly polymorphic MSP2 was used for vaccination, we examined whether the elicited response was directed against conserved or strain-specific epitopes. Postvaccination (week 12) titers of antibody against recombinantly expressed individual domains of MSP2 were measured by enzyme-linked immunosorbent assay and compared to baseline values. We found that vaccination with the 3D7 form of MSP2 induced a significant strain-specific humoral response directed against the repetitive and semiconserved family-specific part. The conserved N- and C-terminal domains were not immunogenic. Titers of antibody against the alternate FC27 family-specific domain showed a tendency to increase in vaccinated children, but there was no increase in antibodies against FC27-type 32-mer repeats. These results indicate that vaccination with one MSP2 variant mainly induced a strain-specific response, which can explain the selective effect of vaccination with combination B on the genotypes of breakthrough parasites. These findings support the inclusion of both family-specific domains (3D7 and FC27) in an improved vaccine formulation.
authors.affiliation: Swiss Tropical Institute, Socinstrasse 57, Basel.
authors.forename: Christian
authors.initials: C
authors.lastname: Flück
authors.forename: Tom
authors.initials: T
authors.lastname: Smith
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Beck
authors.forename: Andrea
authors.initials: A
authors.lastname: Irion
authors.forename: Inoni
authors.initials: I
authors.lastname: Betuela
authors.forename: Michael P
authors.initials: MP
authors.lastname: Alpers
authors.forename: Robin
authors.initials: R
authors.lastname: Anders
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
authors.forename: Blaise
authors.initials: B
authors.lastname: Genton
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D006801:Humans; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control; D009512:New Guinea; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D010963:Plasmodium falciparum / Q000145:classification / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013045:Species Specificity; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D010455:Peptides; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C065974:merozoite surface protein 2, Plasmodium