Human immune responses to the highly repetitive Plasmodium falciparum antigen Pf332.

Kulane, Asli; Siddique, Abu Bakar; Sarthou, Jean-Louis; Tall, Adama; Dièye, Alioune; Perlmann, Hedvig; Perlmann, Peter; Ahlborg, Niklas

doi:10.4269/ajtmh.1999.61.141

Cited by 10 publications

(7 citation statements)

References 49 publications

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“…Many of the EB200‐derived peptides were well recognized in ELISA by sera from Liberian and Senegalese adults analysed herein. The reactivity pattern was similar to that seen in a previous study, analysing a limited number of adult sera from Senegal [36]. The finding that certain peptides were more frequently recognized than others suggests that some of the degenerate repeats of Pf332 form immunogenically and/or antigenically more attractive B‐cell epitopes.…”

Section: Discussionsupporting

confidence: 85%

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Antibody responses to the repetitivePlasmodium falciparumantigen Pf332 in humans naturally primed to the parasite

Ahlborg

Haddad

Siddique

et al. 2002

Clinical and Experimental Immunology

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SUMMARYAntibodies 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 nonresponsiveness 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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Section: Discussionsupporting

confidence: 85%

“…Thus, poor reactivity with EB200 in adults is likely to reflect a low degree of recent exposure to malaria rather than a marked low responsiveness to Pf332. Moreover, when T‐cell responses to EB200 were analysed in donors from Dielmo, no correlation between low or high responsiveness with particular HLA molecules was found [36].…”

Section: Discussionmentioning

confidence: 94%

Antibody responses to the repetitivePlasmodium falciparumantigen Pf332 in humans naturally primed to the parasite

Ahlborg

Haddad

Siddique

et al. 2002

Clinical and Experimental Immunology

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“…Measurement of antibodies against asexual blood‐stage antigens by ELISA. Plasma samples were tested for P. falciparum ‐specific IgE, IgM, IgG and IgG subclasses by standard indirect enzyme‐linked immunosorbent assays (ELISA) with modifications from those previously described [25, 26]. Briefly, EIA/RIA plates (Costar, Cambridge, MA, USA) were coated overnight at 4 °C with 50 μ l/well of crude percoll‐enriched lysate of parasite‐infected erythrocyte F32 antigen (10 μ g/ml) or recombinant Pf332‐C231 (5 μ g/ml) diluted in sodium carbonate buffer (pH 9.6).…”

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confidence: 99%

Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood‐stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients

et al. 2007

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In a prospective clinical study in New Halfa Teaching Hospital, the possible association between FcγRIIa‐R/H131 polymorphism and anti‐malarial antibody responses with clinical outcome of Plasmodium falciparum malaria among Sudanese patients was investigated. A total of 256 individuals were consecutively enrolled, comprising 115 patients with severe malaria, 85 with mild malaria and 56 malaria‐free controls. Genotyping of FcγRIIa‐R/H131 dimorphism was performed using gene‐specific polymerase chain reaction (PCR) amplification with allele‐specific restriction enzyme digestion of the PCR product. The antibody responses to asexual blood‐stage antigens were assessed by an enzyme‐linked immunosorbent assay. The frequency of the FcγRIIa‐R/R131 genotype was significantly higher in those with severe malaria when compared with patients with mild malaria, while the FcγRIIa‐H/H131 genotype showed a significant association with mild malaria. A reduced risk of severe malaria with IgG3 antibodies in combination with the H/H131 genotype was observed. Furthermore, low levels of IgG2 antibodies reactive with the Pf332‐C231 antigen were also associated with lower risk of severe malaria in individuals carrying the H131 allele. The levels of IgG1 and IgG3 antibodies were statistically significantly higher in the mild malaria patients when compared with the severe malaria patients. Taken together, our study revealed that the FcγRIIa‐R/R131 genotype is associated with the development of severe malaria, while the H/H131 genotype is more likely to be associated with mild malaria. Our results also revealed that the natural acquisition of immunity against clinical malaria appeared to be more associated with IgG1 and IgG3 antibodies, signifying their roles in parasite‐neutralizing immune mechanisms.

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“…B13 protein is recognized by IgG serum antibodies from 97% of T. cruzi infected individuals in Latin America, bearing both forms of chronic Chagas' disease: chronic Chagas' disease cardiomyopathy (CCC) and the asymptomatic/indeterminate form (ASY) [8, 9]. Indeed, there is evidence supporting that the antibody response towards repetitive protozoan antigens is T cell-independent [10, 11]. …”

Section: Introductionmentioning

confidence: 99%

Evidence for T Cell Help in the IgG Response against Tandemly RepetitiveTrypanosoma cruziB13 Protein in Chronic Chagas Disease Patients

Duranti

Camargo

Victora

et al. 2012

Journal of Parasitology Research

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The tandemly repetitive Trypanosoma cruzi B13 protein is an immunodominant antigen among Chagas disease patients. Such repetitive domains may behave as T-independent antigens. However, T cells can recognize B13 epitopes in an HLA class II-restricted fashion and could potentially provide cognate T cell help and boost antibody titers. We assessed whether the presence of HLA class II molecules able to present B13 epitopes to T cells could affect anti-B13 IgG levels in a cognate fashion, in both major clinical forms of chronic Chagas disease. We found no difference between anti-B13 IgG antibody levels between patients carrying HLA class II molecules associated to T cell responses or other alleles. The predominant anti-B13 IgG subclass was IgG1, with negligible IgG2, suggesting a T-dependent, noncognate help for antibody production. In addition, the finding of increased anti-B13 IgG levels in sera from CCC patients indicates that clinical presentation is associated with increased anti-B13 antibody levels.

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Human immune responses to the highly repetitive Plasmodium falciparum antigen Pf332.

Cited by 10 publications

References 49 publications

Antibody responses to the repetitivePlasmodium falciparumantigen Pf332 in humans naturally primed to the parasite

Antibody responses to the repetitivePlasmodium falciparumantigen Pf332 in humans naturally primed to the parasite

Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood‐stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients

Evidence for T Cell Help in the IgG Response against Tandemly RepetitiveTrypanosoma cruziB13 Protein in Chronic Chagas Disease Patients

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