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The Plasmodium falciparum merozoite surface protein-1 19 KD antibody response in the Peruvian Amazon predominantly targets the non-allele specific, shared sites of this antigen.

Sutton PL, Clark EH, Silva C, Branch OH - Malar. J. (2010)

Bottom Line: The immuno-depletion ELISAs showed all samples responded to the antigenic sites shared amongst all allelic forms of PfMSP1-19KD.This has important implications for the use of PfMSP1-19KD as a vaccine candidate.Alternatively, these allelic polymorphisms are not immune-specific even in other geographic regions, implying these polymorphisms may be less important in immune evasion that previous studies suggest.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Parasitology, New York University, New York, New York, USA.

ABSTRACT

Background: Plasmodium falciparum re-emerged in Iquitos, Peru in 1994 and is now hypoendemic (< 0.5 infections/person/year). Purportedly non-immune individuals with discrete (non-overlapping) P. falciparum infections can be followed using this population dynamic. Previous work demonstrated a strong association between this population's antibody response to PfMSP1-19KD and protection against febrile illness and parasitaemia. Therefore, some selection for PfMSP1-19KD allelic diversity would be expected if the protection is to allele-specific sites of PfMSP1-19KD. Here, the potential for allele-specific polymorphisms in this population is investigated, and the allele-specificity of antibody responses to PfMSP1-19KD are determined.

Methods: The 42KD region in PfMSP1 was genotyped from 160 individual infections collected between 2003 and 2007. Additionally, the polymorphic block 2 region of Pfmsp1 (Pfmsp1-B2) was genotyped in 781 infection-months to provide a baseline for population-level diversity. To test whether PfMSP1-19KD genetic diversity had any impact on antibody responses, ELISAs testing IgG antibody response were performed on individuals using all four allele-types of PfMSP1-19KD. An antibody depletion ELISA was used to test the ability of antibodies to cross-react between allele-types.

Results: Despite increased diversity in Pfmsp1-B2, limited diversity within Pfmsp1-42KD was observed. All 160 infections genotyped were Mad20-like at the Pfmsp1-33KD locus. In the Pfmsp1-19KD locus, 159 (99.4%) were the Q-KSNG-F haplotype and 1 (0.6%) was the E-KSNG-L haplotype. Antibody responses in 105 individuals showed that Q-KNG and Q-TSR alleles generated the strongest immune responses, while Q-KNG and E-KNG responses were more concordant with each other than with those from Q-TSR and E-TSR, and vice versa. The immuno-depletion ELISAs showed all samples responded to the antigenic sites shared amongst all allelic forms of PfMSP1-19KD.

Conclusions: A non-allele specific antibody response in PfMSP1-19KD may explain why other allelic forms have not been maintained or evolved in this population. This has important implications for the use of PfMSP1-19KD as a vaccine candidate. It is possible that Peruvians have increased antibody responses to the shared sites of PfMSP1-19KD, either due to exposure/parasite characteristics or due to a human-genetic predisposition. Alternatively, these allelic polymorphisms are not immune-specific even in other geographic regions, implying these polymorphisms may be less important in immune evasion that previous studies suggest.

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Immunodepletion results. The mean residual antibody OD values are shown on the y-axis, antigens that underwent immunodepletion are shown on the z-axis, and secondary antibody responses are shown on the x-axis. The range for all samples was 0.019-0.142. The standard error of most comparisons was low (with a range of 0.00-0.05), and so not shown on this graphic.
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Figure 4: Immunodepletion results. The mean residual antibody OD values are shown on the y-axis, antigens that underwent immunodepletion are shown on the z-axis, and secondary antibody responses are shown on the x-axis. The range for all samples was 0.019-0.142. The standard error of most comparisons was low (with a range of 0.00-0.05), and so not shown on this graphic.

Mentions: Patient sera depleted with the Q-KNG allele-type did not have a positive antibody response remaining to any of the four allele-types, indicating that there was not a -TSR or E- specific antibody response. With respect to the Q- or -KNG specific responses, it was observed that there remained a strong E-KNG response in eight of the 18 individuals after depleting with Q-TSR, and, similarly, after depleting with E-KNG 7 of the 18 individuals had a Q-TSR antibody response. Considering all the allele-specific antibody depletion permutations (as shown in Figure 4), after antibody depletion with Q- and/or -TSR allelic forms, 14 individuals had antibody responses. Of these 14 individuals, 11 had both -KNG and Q- specific responses while all 14 had Q- specific antibody responses (even in the absence of the -KNG). Figure 4 shows the mean antibody level after each of the antibody depletions.


The Plasmodium falciparum merozoite surface protein-1 19 KD antibody response in the Peruvian Amazon predominantly targets the non-allele specific, shared sites of this antigen.

Sutton PL, Clark EH, Silva C, Branch OH - Malar. J. (2010)

Immunodepletion results. The mean residual antibody OD values are shown on the y-axis, antigens that underwent immunodepletion are shown on the z-axis, and secondary antibody responses are shown on the x-axis. The range for all samples was 0.019-0.142. The standard error of most comparisons was low (with a range of 0.00-0.05), and so not shown on this graphic.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2818648&req=5

Figure 4: Immunodepletion results. The mean residual antibody OD values are shown on the y-axis, antigens that underwent immunodepletion are shown on the z-axis, and secondary antibody responses are shown on the x-axis. The range for all samples was 0.019-0.142. The standard error of most comparisons was low (with a range of 0.00-0.05), and so not shown on this graphic.
Mentions: Patient sera depleted with the Q-KNG allele-type did not have a positive antibody response remaining to any of the four allele-types, indicating that there was not a -TSR or E- specific antibody response. With respect to the Q- or -KNG specific responses, it was observed that there remained a strong E-KNG response in eight of the 18 individuals after depleting with Q-TSR, and, similarly, after depleting with E-KNG 7 of the 18 individuals had a Q-TSR antibody response. Considering all the allele-specific antibody depletion permutations (as shown in Figure 4), after antibody depletion with Q- and/or -TSR allelic forms, 14 individuals had antibody responses. Of these 14 individuals, 11 had both -KNG and Q- specific responses while all 14 had Q- specific antibody responses (even in the absence of the -KNG). Figure 4 shows the mean antibody level after each of the antibody depletions.

Bottom Line: The immuno-depletion ELISAs showed all samples responded to the antigenic sites shared amongst all allelic forms of PfMSP1-19KD.This has important implications for the use of PfMSP1-19KD as a vaccine candidate.Alternatively, these allelic polymorphisms are not immune-specific even in other geographic regions, implying these polymorphisms may be less important in immune evasion that previous studies suggest.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Parasitology, New York University, New York, New York, USA.

ABSTRACT

Background: Plasmodium falciparum re-emerged in Iquitos, Peru in 1994 and is now hypoendemic (< 0.5 infections/person/year). Purportedly non-immune individuals with discrete (non-overlapping) P. falciparum infections can be followed using this population dynamic. Previous work demonstrated a strong association between this population's antibody response to PfMSP1-19KD and protection against febrile illness and parasitaemia. Therefore, some selection for PfMSP1-19KD allelic diversity would be expected if the protection is to allele-specific sites of PfMSP1-19KD. Here, the potential for allele-specific polymorphisms in this population is investigated, and the allele-specificity of antibody responses to PfMSP1-19KD are determined.

Methods: The 42KD region in PfMSP1 was genotyped from 160 individual infections collected between 2003 and 2007. Additionally, the polymorphic block 2 region of Pfmsp1 (Pfmsp1-B2) was genotyped in 781 infection-months to provide a baseline for population-level diversity. To test whether PfMSP1-19KD genetic diversity had any impact on antibody responses, ELISAs testing IgG antibody response were performed on individuals using all four allele-types of PfMSP1-19KD. An antibody depletion ELISA was used to test the ability of antibodies to cross-react between allele-types.

Results: Despite increased diversity in Pfmsp1-B2, limited diversity within Pfmsp1-42KD was observed. All 160 infections genotyped were Mad20-like at the Pfmsp1-33KD locus. In the Pfmsp1-19KD locus, 159 (99.4%) were the Q-KSNG-F haplotype and 1 (0.6%) was the E-KSNG-L haplotype. Antibody responses in 105 individuals showed that Q-KNG and Q-TSR alleles generated the strongest immune responses, while Q-KNG and E-KNG responses were more concordant with each other than with those from Q-TSR and E-TSR, and vice versa. The immuno-depletion ELISAs showed all samples responded to the antigenic sites shared amongst all allelic forms of PfMSP1-19KD.

Conclusions: A non-allele specific antibody response in PfMSP1-19KD may explain why other allelic forms have not been maintained or evolved in this population. This has important implications for the use of PfMSP1-19KD as a vaccine candidate. It is possible that Peruvians have increased antibody responses to the shared sites of PfMSP1-19KD, either due to exposure/parasite characteristics or due to a human-genetic predisposition. Alternatively, these allelic polymorphisms are not immune-specific even in other geographic regions, implying these polymorphisms may be less important in immune evasion that previous studies suggest.

Show MeSH
Related in: MedlinePlus