Effect of the malaria vaccine Combination B on merozoite surface antigen 2 diversity

Details

Serval ID
serval:BIB_85131743346C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effect of the malaria vaccine Combination B on merozoite surface antigen 2 diversity
Journal
Infection, Genetics and Evolution
Author(s)
Fluck  C., Schopflin  S., Smith  T., Genton  B., Alpers  M. P., Beck  H. P., Felger  I.
ISSN
1567-1348 (Print)
Publication state
Published
Issued date
01/2007
Volume
7
Number
1
Pages
44-51
Notes
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Abstract
Extensive genetic polymorphism is generally found in Plasmodium falciparum surface antigens. This poses a considerable obstacle to the development of a malaria vaccine. In order to assess possible effects of a polymorphic vaccine, we have analyzed the genetic diversity of parasites collected in the course of a phase 2b field trial of the blood stage vaccine Combination B in Papua New Guinea. The full-length 3D7 allele of the merozoite surface protein 2 (MSP2) was included in Combination B as one of three subunits. Vaccinees had a lower prevalence of parasites carrying a 3D7-type allele (corresponding to that in the vaccine) and selection appeared to favour the alternative FC27-type alleles resulting in a higher incidence of morbid episodes associated with FC27-type parasites. We sequenced MSP2 alleles detected in study participants after vaccination to identify breakthrough genotypes. Extensive genetic diversity of MSP2 was observed in both the repetitive and family-specific domains, but alleles occurring in vaccine recipients were no different from those found in placebo recipients. A phylogenetic analysis showed no clustering of 3D7-type breakthrough infections from vaccine recipients. The repeat unit present in the vaccine molecule occurred in a number of alleles from the trial area and was also observed in vaccinated individuals. Thus the anti-repeat immune response did not lead to elimination of parasites carrying the same repeat unit. We conclude that the conserved epitopes in the family-specific domain were the most important determinants of the vaccine effect against new 3D7-type infections and that the hypervariable domains were not subject to selective effects of the vaccine.
Keywords
Animals Antigens, Protozoan/chemistry/*genetics Child Child, Preschool Cross-Sectional Studies Humans Malaria Vaccines/*administration & dosage/immunology Malaria, Falciparum/epidemiology/immunology Phylogeny Plasmodium falciparum/*drug effects/genetics/immunology Protozoan Proteins/chemistry/*genetics Sequence Analysis, DNA Vaccines, Synthetic/immunology Variation (Genetics)/*drug effects
Pubmed
Web of science
Create date
28/01/2008 12:49
Last modification date
20/08/2019 15:44
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