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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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IgM responses to MSP1 Block 4 and Blocks 16-17. (A) Seroprevalence based on n = 111 Colombian, n = 22 Papua New Guinean and n = 72 Cameroonian samples. (B) Mean antibody levels (MFI units) for positive samples. Error bars correspond to the standard error of the mean.
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Figure 1: IgM responses to MSP1 Block 4 and Blocks 16-17. (A) Seroprevalence based on n = 111 Colombian, n = 22 Papua New Guinean and n = 72 Cameroonian samples. (B) Mean antibody levels (MFI units) for positive samples. Error bars correspond to the standard error of the mean.

Mentions: Overall, seroprevalences ranged from 10 to 42% for individual peptides (Figure 1A), with 32% to 44% of individuals within each of the three populations having IgM antibodies to one or more block 4 peptide (Figure 1A). For comparison, the seroprevalence of IgM antibodies to blocks 16-17 ranged from 35% to 65% (Figure 1A). Within each population, the prevalence of IgM antibodies to each of the four block 4 peptides was similar, i.e., ~35% in Colombians, 10% in female adults in PNG, and 25% in Cameroonians. Additionally, when individuals had IgM antibodies against one peptide, their sera usually reacted with the other three peptides as well, suggesting cross-reactive epitopes shared among the peptides.


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)

IgM responses to MSP1 Block 4 and Blocks 16-17. (A) Seroprevalence based on n = 111 Colombian, n = 22 Papua New Guinean and n = 72 Cameroonian samples. (B) Mean antibody levels (MFI units) for positive samples. Error bars correspond to the standard error of the mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: IgM responses to MSP1 Block 4 and Blocks 16-17. (A) Seroprevalence based on n = 111 Colombian, n = 22 Papua New Guinean and n = 72 Cameroonian samples. (B) Mean antibody levels (MFI units) for positive samples. Error bars correspond to the standard error of the mean.
Mentions: Overall, seroprevalences ranged from 10 to 42% for individual peptides (Figure 1A), with 32% to 44% of individuals within each of the three populations having IgM antibodies to one or more block 4 peptide (Figure 1A). For comparison, the seroprevalence of IgM antibodies to blocks 16-17 ranged from 35% to 65% (Figure 1A). Within each population, the prevalence of IgM antibodies to each of the four block 4 peptides was similar, i.e., ~35% in Colombians, 10% in female adults in PNG, and 25% in Cameroonians. Additionally, when individuals had IgM antibodies against one peptide, their sera usually reacted with the other three peptides as well, suggesting cross-reactive epitopes shared among the peptides.

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