Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4

Malar J. 2010 Jan 13;9:14. doi: 10.1186/1475-2875-9-14.

Abstract

Background: Plasmodium falciparum merozoite surface protein-1 (MSP1) has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17) and the hypervariable N-terminal repeat region (block 2). However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene.

Methods: The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7) in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition.

Results: IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%), with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations.

Conclusions: Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to P. falciparum is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important in isolate-specific immunity to P. falciparum.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Antibodies, Protozoan / genetics
  • Antibodies, Protozoan / immunology
  • Cameroon
  • Child
  • Child, Preschool
  • Colombia
  • Cross Reactions / genetics
  • Cross Reactions / immunology
  • Epitopes / genetics
  • Epitopes / immunology*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology*
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology*
  • Infant
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / transmission
  • Male
  • Merozoite Surface Protein 1 / genetics*
  • Merozoite Surface Protein 1 / immunology
  • Merozoite Surface Protein 1 / metabolism
  • Middle Aged
  • Papua New Guinea
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Young Adult

Substances

  • Antibodies, Protozoan
  • Epitopes
  • Immunoglobulin G
  • Immunoglobulin M
  • Merozoite Surface Protein 1
  • Recombinant Proteins