Measurement of Antibody Levels against Region II of the Erythrocyte-Binding Antigen 175 of Plasmodium falciparum in an Area of Malaria Holoendemicity in Western Kenya (original) (raw)
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Analysis of Human Antibodies to Erythrocyte Binding Antigen 175 of Plasmodium falciparum
Infection and Immunity, 2000
Plasmodium falciparum merozoites is a multistep process. For many strains of the parasite, part of this process requires that the erythrocyte binding antigen 175 (EBA-175) of the merozoite binds to sialic acid residues of glycophorin A on the erythrocyte surface, a receptor-ligand interaction which represents a potential target for inhibition by antibodies. This study characterizes the reactivity of naturally acquired human antibodies with four recombinant proteins representing parts of EBA-175 (region II, regions III to V, and the dimorphic C and F segment region) in populations in which the organism is endemic. Serum immunoglobulin G (IgG) recognizing the recombinant proteins is predominantly of the IgG1 and IgG3 subclasses, and its prevalence increases with age. In a large population study in The Gambia, serum positivity for IgG or IgG1 and IgG3 subclass antibodies to each of the EBA-175 recombinant antigens was not significantly associated with subsequent protection from clinical malaria. However, there was a trend indicating that individuals with high levels of IgG to region II may have some protection.
Malaria journal, 2004
The erythrocyte binding antigen-175 (EBA-175) on Plasmodium falciparum merozoites mediates sialic acid dependent binding to glycophorin A on host erythrocytes and, therefore, plays a crucial role in cell invasion. Dimorphic allele segments have been found in its encoding gene with a 342 bp segment present in FCR-3 strains (F-segment) and a 423 bp segment in CAMP strains (C-segment). Possible associations of the dimorphism with severe malaria have been analysed in a case-control study in northern Ghana. Blood samples of 289 children with severe malaria and 289 matched parasitaemic but asymptomatic controls were screened for eba-175 F- and C-segments by nested polymerase chain reaction. In children with severe malaria, prevalences of F-, C- and mixed F-/C-segments were 70%, 19%, and 11%, respectively. The C-segment was found more frequently in severe malaria cases whereas mixed infections were more common in controls. Infection with strains harbouring the C-segment significantly incre...
Erythrocyte Invasion Phenotypes of Plasmodiumfalciparum in The Gambia
Infection and Immunity, 2003
In vitro experimentation with Plasmodium falciparum has determined that a number of different receptorligand interactions are involved in the invasion of erythrocytes. Most culture-adapted parasite isolates use a mechanism of invasion that depends primarily on the erythrocyte sialoglycoprotein glycophorin A (GYPA) and erythrocyte-binding antigen 175 (EBA-175) of the parasite blood-stage merozoite. However, a minority of culture-adapted parasites and a majority of Indian field isolates can apparently invade by other means. Here, erythrocyte invasion phenotypes of P. falciparum field isolates in Africa were studied. For 38 Gambian isolates, invasion of neuraminidase-treated and trypsin-treated erythrocytes was inhibited, on average, by more than 60 and 85%, respectively, indicating a high level of dependence on sialic acid and trypsin-sensitive proteins on the erythrocyte surface. These results support the hypothesis that African P. falciparum parasites use GYPA as a primary receptor for invasion. However, the considerable variation among isolates confirms the idea that alternative receptors are also used by many parasites. Three amino acid polymorphisms in the GYPA-binding region of EBA-175 (region II) were not significantly associated with invasion phenotype. There was variation among isolates in the selectivity index (i.e., a statistical tendency toward aggregation or multiple invasions of host erythrocytes), but this variation did not correlate with enzyme-determined invasion phenotype or with eba-175 alleles. Overall, these invasion phenotypes in Africa support a vaccine strategy of inhibiting EBA-175 binding to GYPA but suggest that parasites with alternative phenotypes would be selected for if this strategy were used alone.
Immunology Letters, 2000
In areas of unstable transmission malaria affects all age groups, but the malaria incidence is lower in adults compared to children and teenagers. Under such conditions subclinical Plasmodium falciparum infections are common and some infections are controlled, because blood parasitaemia is maintained at low densities. Here, we test the hypothesis that the presence or absence of antibodies against variant antigens on the surface of P. falciparum-infected erythrocytes protect individuals against some infectious challenges and render them susceptible to others. Plasma collected in Daraweesh, eastern Sudan, before and after the malaria season from individuals who had (susceptible) or did not have malaria (protected) during the season, were tested for reactivity against variant antigens on the surface of nine parasite isolates by flow cytometry. Both protected and susceptible individuals acquired antibodies to variant antigens during the malaria season. The presence of antibody to a Ghanaian isolate before the season was statistically significantly associated with protection against malaria. When considering all nine isolates, the patterns of antibody acquisition differed between susceptible and protected individuals. Together, the results indicate that pre-existing anti-PfEMP1 antibodies can reduce the risk of contracting clinical malaria when challenged by novel parasite clones expressing homologous, but not heterologous variable surface antigens. The results also confirm that antibodies to variant antigens are induced by both clinical and subclinical infections, and that antibodies against several 6ar sero-types are induced during an infection.
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Malaria Journal, 2018
Background: Recent global reports on malaria suggest significant decrease in disease severity and an increase in control interventions in many malaria endemic countries, including Ghana. However, a major driving force sustaining malaria transmission in recent times is the asymptomatic carriage of malaria parasites, which can enhance immune responses against parasite antigens. This study determined the prevalence and relative avidities of naturally induced antibodies to EBA175RIII-V Ll in asymptomatic children living in two communities with varying malaria transmission patterns. Methods: An asexual stage Plasmodium falciparum antigen, EBA175RIII-V Ll was expressed in Lactococcus lactis, purified and used in indirect ELISA to measure total and cytophilic IgG concentrations and avidities in children aged between 6 and 12 years. The children were selected from Obom and Abura, communities with perennial and seasonal malaria transmission, respectively. Venous blood samples were collected in July and October 2015 and again in January 2016. The multiplicity of infection and the genetic diversity of EBA175RIII circulating in both sites were also assessed using polymerase chain reaction. Results: Asymptomatic parasite carriage in the children from Obom decreased from July (peak season), through October and January, however parasite carriage in children from Abura was bimodal, with the lowest prevalence estimated in October. Antibody concentrations over the course of the study remained stable within each study site however, children living in Obom had significantly higher EBA175RIII-V Ll antibody concentrations than children living in Abura (P < 0.05, Mann-Whitney test). Over the course of the study, the relative antibody avidities of EBA175RIII-V Ll IgG antibodies were similar within and between the sites. Conclusion: Naturally acquired IgG concentrations but not relative antibody avidities to EBA175RIII-V were significantly higher in Obom where malaria transmission is perennial than in Abura, where malaria transmission is seasonal.