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. 2002 Aug;129(2):318-25.
doi: 10.1046/j.1365-2249.2002.01891.x.

Antibody responses to the repetitive Plasmodium falciparum antigen Pf332 in humans naturally primed to the parasite

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Antibody responses to the repetitive Plasmodium falciparum antigen Pf332 in humans naturally primed to the parasite

N Ahlborg et al. Clin Exp Immunol. 2002 Aug.

Abstract

Antibodies to the degenerate repeats of EB200, a part of the Plasmodium falciparum antigen Pf332, are protective in monkeys. To analyse the prevalence, magnitude and specificity of antibodies to EB200 in malaria-exposed humans, the IgG antibody reactivity with recombinant EB200 protein as well as with crude malaria antigen was determined in Senegalese donors (n = 100; 4-87 years). Antibody reactivity with EB200 was low or absent in children below 15 years but was prevalent and significantly higher in older donors. In comparison, all individuals displayed reactivity with a crude malaria antigen preparation, which also increased with age. The reactivity with the crude malaria antigen was correlated to the reactivity with EB200, suggesting that the low levels of IgG to EB200 found in some adult donors reflected a limited degree of recent exposure to parasites rather than a selective non-responsiveness to Pf332. Comparison of serological and clinical data showed that high levels of antibodies to crude malaria antigen and to EB200 were predictive of fewer future clinical attacks of malaria. A reactivity pattern very similar to that found in Senegalese donors was observed in Liberian adults where 80% of the sera showed reactivity with EB200 and all peptides were recognized by between 60 and 100% of the donors. This strong reactivity with EB200-derived overlapping peptides suggests that the epitopes in EB200, to a large extent, are linear. In the light of previous data on the parasite neutralizing capacity of antibodies to Pf332, the present results emphasize the potential interest of Pf332-derived sequences for inclusion in a subunit vaccine against P. falciparum malaria.

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Figures

Fig. 1
Fig. 1
Specificity of rabbit antisera to EB200. Sera from two rabbits immunized with ZZ-EB200 were analysed for reactivity with GST-EB200 and a panel of peptides spanning EB200 (P-1 to -17) in ELISA. GST and the RESA repeat-derived peptide 6 × 4 (EENV)6, were included for comparison. The graph displays reactivity of sera diluted 1 : 500 with one serum indicated by black bars and the other with white bars.
Fig. 2
Fig. 2
Reactivity of sera from Senegalese donors with crude malaria antigen and EB200. Sera from 100 donors were analysed at a dilution of 1 : 1000 for reactivity with crude malaria antigen extract as well as with EB200 (GST-EB200 reactivity minus GST reactivity) in ELISA. The individual donors (4–87 years) are displayed according to age and the different age groups are indicated below the bars. White bars display reactivity with EB200 with absorbance values indicated on the right y-axis. Reactivity with crude malaria antigens is shown as black bars with the absorbance values displayed on the left x-axis. The level of background reactivity of Swedish control sera was 0·150 ± 0·031 (crude malaria antigen), 0·094 ± 0·024 (GST-EB200) and 0·088 ± 0·024 (GST). In cases where the white bars mask the black bars, the height of the black bar is indicated by a horizontal line. □, Recombinant EB200; ▪, crude malaria antigen.
Fig. 3
Fig. 3
Fine specificity of human IgG antibodies reactive with EB200. (a) Sera from 83 Liberian adults were analysed at a dilution of 1 : 1000 for antibody reactivity with EB200 and a panel of peptides together spanning the EB200 sequence in ELISA. The reactivity was defined as percent reactivity of a human immune serum reactive with peptide 6 × 4 and was graded as below cut off, >cut off 15%, >15%–25% and >25%. Cut-off for each ELISA antigen was defined as the mean reactivity of Swedish control sera +3 s.d. (b) Antibodies affinity purified on peptide P-2, -6, -12 or -17 were tested for reactivity with EB200 as well as with P-1 to -17 in ELISA. Reactivity with EB200 and peptides displayed by serum from donor BH147 diluted 1 : 1000 and affinity purified IgG from the same donor diluted 1 : 300. (c) Peptide specificity of antibodies affinity purified on P-17 from donor BD67 and W150, respectively. (b and c) The y axes present the ELISA absorbance values at 405 nm. Reactivities of >50% of the reactivity with the peptide used for purification are indicated with black bars. Reactivities of less than 50% are depicted with white bars. Asterisks indicate the peptide used for purification. □, ≤Cut-off; formula image, <cut-off 15%; formula image, >15–25%; ▪, >25%.

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