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

Chang SP, Kayatani AK, Terrientes ZI, Herrera S, Leke RG, Taylor DW - Malar. J. (2010)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: John A Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo St, Honolulu, HI 96813, USA. sandrac@hawaii.edu

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.

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Mapping of dimorphic allelic IgG MSP1 Block 4 epitopes. Human antibodies that reacted with Block 4-1 and 4-3 (black) and with Block 4-2 and 4-4 (blue) recognized allelic sequences indicated by asterisks within the boxed region.
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Figure 7: Mapping of dimorphic allelic IgG MSP1 Block 4 epitopes. Human antibodies that reacted with Block 4-1 and 4-3 (black) and with Block 4-2 and 4-4 (blue) recognized allelic sequences indicated by asterisks within the boxed region.

Mentions: The IgG block 4 response was specific and clearly discriminated among MSP1 block 4 sequences. A majority of individuals produced IgG antibodies specific for one of the two parental block 4 peptides (i.e., K1 or MAD20) and these antibodies may contribute to isolate-specific immunity to P. falciparum. A subgroup of samples had IgG antibodies that cross-reacted with epitopes shared by one parental and one recombinant allele. Pair-wise comparisons of IgG levels to MSP1 block 4 peptides (Table 1), as well as the specificity of individual samples (Table 2) mapped these two allelic epitopes to dimorphic sequences localized within a 19 amino acid region upstream of the putative block 4 recombination site (Figure 7). However, in all three study populations, IgG antibodies highly specific for the prototype K1 (Block 4-1) and MAD20 (block 4-2) sequences were more prevalent than antibodies recognizing the recombinant (block 4-3 and 4-4) forms.


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

Chang SP, Kayatani AK, Terrientes ZI, Herrera S, Leke RG, Taylor DW - Malar. J. (2010)

Mapping of dimorphic allelic IgG MSP1 Block 4 epitopes. Human antibodies that reacted with Block 4-1 and 4-3 (black) and with Block 4-2 and 4-4 (blue) recognized allelic sequences indicated by asterisks within the boxed region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2837054&req=5

Figure 7: Mapping of dimorphic allelic IgG MSP1 Block 4 epitopes. Human antibodies that reacted with Block 4-1 and 4-3 (black) and with Block 4-2 and 4-4 (blue) recognized allelic sequences indicated by asterisks within the boxed region.
Mentions: The IgG block 4 response was specific and clearly discriminated among MSP1 block 4 sequences. A majority of individuals produced IgG antibodies specific for one of the two parental block 4 peptides (i.e., K1 or MAD20) and these antibodies may contribute to isolate-specific immunity to P. falciparum. A subgroup of samples had IgG antibodies that cross-reacted with epitopes shared by one parental and one recombinant allele. Pair-wise comparisons of IgG levels to MSP1 block 4 peptides (Table 1), as well as the specificity of individual samples (Table 2) mapped these two allelic epitopes to dimorphic sequences localized within a 19 amino acid region upstream of the putative block 4 recombination site (Figure 7). However, in all three study populations, IgG antibodies highly specific for the prototype K1 (Block 4-1) and MAD20 (block 4-2) sequences were more prevalent than antibodies recognizing the recombinant (block 4-3 and 4-4) forms.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: John A Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo St, Honolulu, HI 96813, USA. sandrac@hawaii.edu

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.

Show MeSH
Related in: MedlinePlus