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Published on: August 6, 2020
Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4
Sandra P Chang1, Alexander K K Kayatani, Zilka I Terrientes
1John A Burns School of Medicine, University of Hawaii at Manoa, 651 Ilalo St, Honolulu, HI 96813, USA. sandrac@hawaii.edu
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.
Insights
Immune responses to Plasmodium falciparum merozoite surface protein-1 (MSP1) block 4 were studied in diverse populations. Antibodies to MSP1 block 4 indicate its potential role in isolate-specific immunity to malaria.
Area of Science:
- Immunology
- Malariology
- Genetics
Background:
- Plasmodium falciparum merozoite surface protein-1 (MSP1) is a key malaria vaccine candidate.
- Focus has been on MSP1 C-terminal regions (blocks 16-17) and N-terminal repeats (block 2).
- Emerging evidence suggests other MSP1 regions, like block 4, are under immune selection.
Purpose of the Study:
- To investigate antibody responses to MSP1 block 4.
- To compare responses to block 4 with known regions (blocks 16-17).
- To analyze responses across populations with varying malaria transmission and ethnicity.
Main Methods:
- Examined IgM and IgG antibody responses.
- Utilized parental and recombinant forms of MSP1 block 4 peptides.
- Included study populations from Colombia, Papua New Guinea, and Cameroon.
- Compared responses to blocks 16-17 (3D7).
Main Results:
- IgM and IgG antibodies to MSP1 block 4 were detected in all populations.
- IgG seropositivity to block 4 varied (15-65%) and was lower than to blocks 16-17.
- Antibodies to block 4 showed a bias towards IgG3, while blocks 16-17 favored IgG1.
Conclusions:
- Antibody production to MSP1 block 4 alleles suggests balancing selection by the immune system.
- MSP1 block 4 may contribute to isolate-specific immunity against Plasmodium falciparum.
- Immune responses to block 4 are consistent across low and high malaria transmission areas.
