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

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

Sandra P Chang  1 , Alexander K K Kayatani, Zilka I Terrientes, Socrates Herrera, Rose G F Leke, Diane W Taylor
Affiliations

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

Sandra P Chang et al. Malar J. .

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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Figures

Figure 1
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.
Figure 2
Figure 2
IgG responses to MSP1 Block 4 and Blocks 16-17. (A) Seroprevalence based on n = 111 Colombian, n = 22 Papua New Guinean and n = 64 Cameroonian samples. (B) Mean antibody levels (MFI units) for positive samples. Error bars correspond to standard error of the mean. Significantly different mean MFI values ( P ≤ 0.05) are indicated with an asterisk.
Figure 3
Figure 3
Overall seroprevalence of IgM or IgG antibodies to MSP1 Block 4 and Blocks 16-17. Seroprevalence based on n = 111 Colombian, n = 22 Papua New Guinea and n = 64 Cameroonian samples.
Figure 4
Figure 4
IgG subclass distribution of MSP1 Block 4 and Block 16-17. Sera from samples that contained antibodies to one or more Block 4 peptides (left panel) or Blocks 16-17 (right panel) were assayed for IgG1 and IgG3 isotypes. Colombia (n = 21), Papua New Guinea (n = 9), and Cameroon (n = 11). Clustering of isotype distribution is indicated by ellipses.
Figure 5
Figure 5
IgG subclass responses to MSP1 Block 4 and Blocks 16-17. (A) IgG1 and (B) IgG3 seroprevalences based on n = 21 Colombian, n = 9 Papua New Guinean and n = 11 Cameroonian samples.
Figure 6
Figure 6
Cord Blood IgM responses to MSP1 Block 4 and Blocks 16-17. Mean antibody levels (MFI units) for cord blood samples from Papua New Guinea. Asterisks indicate samples that were above adult cut-off values for the individual peptides.
Figure 7
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.
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