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Comparative analysis of IgG responses to Plasmodium falciparum MSP1p19 and PF13-DBL1α1 using ELISA and a magnetic bead-based duplex assay (MAGPIX®-Luminex) in a Senegalese meso-endemic community.

Perraut R, Richard V, Varela ML, Trape JF, Guillotte M, Tall A, Toure A, Sokhna C, Vigan-Womas I, Mercereau-Puijalon O - Malar. J. (2014)

Bottom Line: Numerous Plasmodium falciparum antigens elicit humoral responses in humans living in endemic areas.Archived plasma samples collected before the rainy season from 217 villagers living in Ndiop, a Senegalese meso-endemic setting, were studied.This may reflect incomplete overlap of the epitopes presented in the two formats.

View Article: PubMed Central - PubMed

Affiliation: Institut Pasteur de Dakar, Unité d'Immunologie, Dakar, Sénégal. perraut@pasteur.sn.

ABSTRACT

Background: Numerous Plasmodium falciparum antigens elicit humoral responses in humans living in endemic areas. Use of multiplex assays is a convenient approach to monitor the antibody response against multiple antigens, but to integrate multiplex assay-derived data with datasets, generated previously using ELISA, comparative studies are needed. This work compares antibody responses to two P. falciparum antigens monitored using both technologies.

Methods: The IgG response against the merozoite surface protein-1 PfMSP1p19 and the PF13-DBL1α1 domain of the P. falciparum Erythrocyte Membrane Protein1, expressed by the rosette-forming parasite 3D7/PF13 (PF13), was investigated using ELISA and a MAGPIX®-Luminex duplex assay. Archived plasma samples collected before the rainy season from 217 villagers living in Ndiop, a Senegalese meso-endemic setting, were studied. ROC analysis was used to define the optimal antibody measure readout. Association of antibody levels with protection against clinical malaria was analysed using Poisson regression in a retrospective study from active case detection records performed during the 5.5-month transmission season that followed blood sampling.

Results: There was a strong positive correlation (P<10(-3)) between ELISA and MAGPIX®-Luminex-MFI (median fluorescence intensity) values for antibody to PfMSP1p19 (rho=0.78) and PF13-DBL1α1 (rho=0.89), with a similar degree of concordance in all age groups. Antibody levels to both antigens were high but displayed a different age-associated pattern. Independent age-adjusted Poisson regression analysis showed a significant association with protection only for IgG responses to MSP1p19 (P<0.01 RR=0.71 [0.53-0.93]) measured by ELISA.

Conclusion: The individual ELISA and duplex-MAGPIX assays provide a concordant evaluation of age-associated antibody responses to MSP1p19 and PF13-DBL1α1, irrespective of the formulation of antibody levels (values, ratios or ROC-adjusted figures) but do diverge with regard to the association of antibody levels with clinical protection in age-adjusted models. This may reflect incomplete overlap of the epitopes presented in the two formats. Further development for multiplex assessment of antibody responses to a larger panel of antigens with the robust and cost effective MAGPIX®-Luminex technology is warranted.

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Incidence of clinical malaria attacks during the 5.5-month follow-up and its relationship to levels of antibody responses against PF13 and MSP1p19. The left panel shows the mean incidence of malaria attacks by age group. The middle and right panels show OD-ratios (black) and MFI-ratios (grey) values of antibody responses to PF13 or MSP1p19 plotted as histograms (+SE) by occurrence of clinical attacks in the follow-up period stratified as 0 vs 1–2 vs >2 confirmed clinical malaria attacks. The number of individuals in each stratified group was 107 (mean age 32.5 [3.9-76.9]), 76 (mean age 19.4 [3.7-74.6]), 34 (mean age 8.7 [3.4-16.1]) with 0 vs 1–2 vs >2 clinical attacks, respectively. Brackets and asterisk indicate significant differences (P < 0.05) between antibody responses in different categories.
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Fig3: Incidence of clinical malaria attacks during the 5.5-month follow-up and its relationship to levels of antibody responses against PF13 and MSP1p19. The left panel shows the mean incidence of malaria attacks by age group. The middle and right panels show OD-ratios (black) and MFI-ratios (grey) values of antibody responses to PF13 or MSP1p19 plotted as histograms (+SE) by occurrence of clinical attacks in the follow-up period stratified as 0 vs 1–2 vs >2 confirmed clinical malaria attacks. The number of individuals in each stratified group was 107 (mean age 32.5 [3.9-76.9]), 76 (mean age 19.4 [3.7-74.6]), 34 (mean age 8.7 [3.4-16.1]) with 0 vs 1–2 vs >2 clinical attacks, respectively. Brackets and asterisk indicate significant differences (P < 0.05) between antibody responses in different categories.

Mentions: A total of 217 individuals were considered for longitudinal follow-up period (1 July-31 December); 229 clinical malaria episodes were recorded. The mean incidence rate of malaria attacks (number of malaria attacks per 100 person-months) was 17.7 (95% CI: [14.6-20.9]). It differed between age groups (Kruskal-Wallis test, P <0.01), with a higher rate (45.8) in the five to nine years group and lower (3.3) in the ≥30 years age group. The cumulative incidence of clinical malaria attacks is shown in Figure 3, left panel, with 24, 108, 51, 33, and 13 clinical malaria episodes recorded in the < five, five to nine, ten to 14, fifteen to29 and ≥30 years age groups, respectively.Figure 3


Comparative analysis of IgG responses to Plasmodium falciparum MSP1p19 and PF13-DBL1α1 using ELISA and a magnetic bead-based duplex assay (MAGPIX®-Luminex) in a Senegalese meso-endemic community.

Perraut R, Richard V, Varela ML, Trape JF, Guillotte M, Tall A, Toure A, Sokhna C, Vigan-Womas I, Mercereau-Puijalon O - Malar. J. (2014)

Incidence of clinical malaria attacks during the 5.5-month follow-up and its relationship to levels of antibody responses against PF13 and MSP1p19. The left panel shows the mean incidence of malaria attacks by age group. The middle and right panels show OD-ratios (black) and MFI-ratios (grey) values of antibody responses to PF13 or MSP1p19 plotted as histograms (+SE) by occurrence of clinical attacks in the follow-up period stratified as 0 vs 1–2 vs >2 confirmed clinical malaria attacks. The number of individuals in each stratified group was 107 (mean age 32.5 [3.9-76.9]), 76 (mean age 19.4 [3.7-74.6]), 34 (mean age 8.7 [3.4-16.1]) with 0 vs 1–2 vs >2 clinical attacks, respectively. Brackets and asterisk indicate significant differences (P < 0.05) between antibody responses in different categories.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4221706&req=5

Fig3: Incidence of clinical malaria attacks during the 5.5-month follow-up and its relationship to levels of antibody responses against PF13 and MSP1p19. The left panel shows the mean incidence of malaria attacks by age group. The middle and right panels show OD-ratios (black) and MFI-ratios (grey) values of antibody responses to PF13 or MSP1p19 plotted as histograms (+SE) by occurrence of clinical attacks in the follow-up period stratified as 0 vs 1–2 vs >2 confirmed clinical malaria attacks. The number of individuals in each stratified group was 107 (mean age 32.5 [3.9-76.9]), 76 (mean age 19.4 [3.7-74.6]), 34 (mean age 8.7 [3.4-16.1]) with 0 vs 1–2 vs >2 clinical attacks, respectively. Brackets and asterisk indicate significant differences (P < 0.05) between antibody responses in different categories.
Mentions: A total of 217 individuals were considered for longitudinal follow-up period (1 July-31 December); 229 clinical malaria episodes were recorded. The mean incidence rate of malaria attacks (number of malaria attacks per 100 person-months) was 17.7 (95% CI: [14.6-20.9]). It differed between age groups (Kruskal-Wallis test, P <0.01), with a higher rate (45.8) in the five to nine years group and lower (3.3) in the ≥30 years age group. The cumulative incidence of clinical malaria attacks is shown in Figure 3, left panel, with 24, 108, 51, 33, and 13 clinical malaria episodes recorded in the < five, five to nine, ten to 14, fifteen to29 and ≥30 years age groups, respectively.Figure 3

Bottom Line: Numerous Plasmodium falciparum antigens elicit humoral responses in humans living in endemic areas.Archived plasma samples collected before the rainy season from 217 villagers living in Ndiop, a Senegalese meso-endemic setting, were studied.This may reflect incomplete overlap of the epitopes presented in the two formats.

View Article: PubMed Central - PubMed

Affiliation: Institut Pasteur de Dakar, Unité d'Immunologie, Dakar, Sénégal. perraut@pasteur.sn.

ABSTRACT

Background: Numerous Plasmodium falciparum antigens elicit humoral responses in humans living in endemic areas. Use of multiplex assays is a convenient approach to monitor the antibody response against multiple antigens, but to integrate multiplex assay-derived data with datasets, generated previously using ELISA, comparative studies are needed. This work compares antibody responses to two P. falciparum antigens monitored using both technologies.

Methods: The IgG response against the merozoite surface protein-1 PfMSP1p19 and the PF13-DBL1α1 domain of the P. falciparum Erythrocyte Membrane Protein1, expressed by the rosette-forming parasite 3D7/PF13 (PF13), was investigated using ELISA and a MAGPIX®-Luminex duplex assay. Archived plasma samples collected before the rainy season from 217 villagers living in Ndiop, a Senegalese meso-endemic setting, were studied. ROC analysis was used to define the optimal antibody measure readout. Association of antibody levels with protection against clinical malaria was analysed using Poisson regression in a retrospective study from active case detection records performed during the 5.5-month transmission season that followed blood sampling.

Results: There was a strong positive correlation (P<10(-3)) between ELISA and MAGPIX®-Luminex-MFI (median fluorescence intensity) values for antibody to PfMSP1p19 (rho=0.78) and PF13-DBL1α1 (rho=0.89), with a similar degree of concordance in all age groups. Antibody levels to both antigens were high but displayed a different age-associated pattern. Independent age-adjusted Poisson regression analysis showed a significant association with protection only for IgG responses to MSP1p19 (P<0.01 RR=0.71 [0.53-0.93]) measured by ELISA.

Conclusion: The individual ELISA and duplex-MAGPIX assays provide a concordant evaluation of age-associated antibody responses to MSP1p19 and PF13-DBL1α1, irrespective of the formulation of antibody levels (values, ratios or ROC-adjusted figures) but do diverge with regard to the association of antibody levels with clinical protection in age-adjusted models. This may reflect incomplete overlap of the epitopes presented in the two formats. Further development for multiplex assessment of antibody responses to a larger panel of antigens with the robust and cost effective MAGPIX®-Luminex technology is warranted.

Show MeSH
Related in: MedlinePlus