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The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children
BACKGROUND: The capacity of Plasmodium falciparum-infected erythrocytes to bind uninfected erythrocytes (rosetting) is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of t...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2959068/ https://www.ncbi.nlm.nih.gov/pubmed/20923548 http://dx.doi.org/10.1186/1475-2875-9-267 |
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author | Vigan-Womas, Inès Lokossou, Adjimon Guillotte, Micheline Juillerat, Alexandre Bentley, Graham Garcia, André Mercereau-Puijalon, Odile Migot-Nabias, Florence |
author_facet | Vigan-Womas, Inès Lokossou, Adjimon Guillotte, Micheline Juillerat, Alexandre Bentley, Graham Garcia, André Mercereau-Puijalon, Odile Migot-Nabias, Florence |
author_sort | Vigan-Womas, Inès |
collection | PubMed |
description | BACKGROUND: The capacity of Plasmodium falciparum-infected erythrocytes to bind uninfected erythrocytes (rosetting) is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of the response to rosette-forming parasites and their PfEMP1 adhesive domains is essential for understanding the acquisition of protection against severe malaria. To this end, the antibody response to a rosetting variant was analysed in children recruited with severe or uncomplicated malaria or asymptomatic P. falciparum infection. METHODS: Serum was collected from Beninese children with severe malaria, uncomplicated malaria or P. falciparum asymptomatic infection (N = 65, 37 and 52, respectively) and from immune adults (N = 30) living in the area. Infected erythrocyte surface-reactive IgG, rosette disrupting antibodies and IgG to the parasite crude extract were analysed using the single variant Palo Alto VarO-infected line. IgG, IgG1 and IgG3 to PfEMP1-varO-derived NTS-DBL1α(1), CIDRγ and DBL2βC2 recombinant domains were analysed by ELISA. Antibody responses were compared in the clinical groups. Stability of the response was studied using a blood sampling collected 14 months later from asymptomatic children. RESULTS: Seroprevalence of erythrocyte surface-reactive IgG was high in adults (100%) and asymptomatic children (92.3%) but low in children with severe or uncomplicated malaria (26.1% and 37.8%, respectively). The IgG, IgG1 and IgG3 antibody responses to the varO-derived PfEMP1 domains were significantly higher in asymptomatic children than in children with clinical malaria in a multivariate analysis correcting for age and parasite density at enrolment. They were essentially stable, although levels tended to decrease with time. VarO-surface reactivity correlated positively with IgG reactivity to the rosetting domain varO-NTS-DBL1α(1). None of the children sera, including those with surface-reactive antibodies possessed anti-VarO-rosetting activity, and few adults had rosette-disrupting antibodies. CONCLUSIONS: Children with severe and uncomplicated malaria had similar responses. The higher prevalence and level of VarO-reactive antibodies in asymptomatic children compared to children with malaria is consistent with a protective role for anti-VarO antibodies against clinical falciparum malaria. The mechanism of such protection seems independent of rosette-disruption, suggesting that the cytophilic properties of antibodies come into play. |
format | Text |
id | pubmed-2959068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29590682010-10-22 The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children Vigan-Womas, Inès Lokossou, Adjimon Guillotte, Micheline Juillerat, Alexandre Bentley, Graham Garcia, André Mercereau-Puijalon, Odile Migot-Nabias, Florence Malar J Research BACKGROUND: The capacity of Plasmodium falciparum-infected erythrocytes to bind uninfected erythrocytes (rosetting) is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of the response to rosette-forming parasites and their PfEMP1 adhesive domains is essential for understanding the acquisition of protection against severe malaria. To this end, the antibody response to a rosetting variant was analysed in children recruited with severe or uncomplicated malaria or asymptomatic P. falciparum infection. METHODS: Serum was collected from Beninese children with severe malaria, uncomplicated malaria or P. falciparum asymptomatic infection (N = 65, 37 and 52, respectively) and from immune adults (N = 30) living in the area. Infected erythrocyte surface-reactive IgG, rosette disrupting antibodies and IgG to the parasite crude extract were analysed using the single variant Palo Alto VarO-infected line. IgG, IgG1 and IgG3 to PfEMP1-varO-derived NTS-DBL1α(1), CIDRγ and DBL2βC2 recombinant domains were analysed by ELISA. Antibody responses were compared in the clinical groups. Stability of the response was studied using a blood sampling collected 14 months later from asymptomatic children. RESULTS: Seroprevalence of erythrocyte surface-reactive IgG was high in adults (100%) and asymptomatic children (92.3%) but low in children with severe or uncomplicated malaria (26.1% and 37.8%, respectively). The IgG, IgG1 and IgG3 antibody responses to the varO-derived PfEMP1 domains were significantly higher in asymptomatic children than in children with clinical malaria in a multivariate analysis correcting for age and parasite density at enrolment. They were essentially stable, although levels tended to decrease with time. VarO-surface reactivity correlated positively with IgG reactivity to the rosetting domain varO-NTS-DBL1α(1). None of the children sera, including those with surface-reactive antibodies possessed anti-VarO-rosetting activity, and few adults had rosette-disrupting antibodies. CONCLUSIONS: Children with severe and uncomplicated malaria had similar responses. The higher prevalence and level of VarO-reactive antibodies in asymptomatic children compared to children with malaria is consistent with a protective role for anti-VarO antibodies against clinical falciparum malaria. The mechanism of such protection seems independent of rosette-disruption, suggesting that the cytophilic properties of antibodies come into play. BioMed Central 2010-10-05 /pmc/articles/PMC2959068/ /pubmed/20923548 http://dx.doi.org/10.1186/1475-2875-9-267 Text en Copyright ©2010 Vigan-Womas et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Vigan-Womas, Inès Lokossou, Adjimon Guillotte, Micheline Juillerat, Alexandre Bentley, Graham Garcia, André Mercereau-Puijalon, Odile Migot-Nabias, Florence The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children |
title | The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children |
title_full | The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children |
title_fullStr | The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children |
title_full_unstemmed | The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children |
title_short | The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children |
title_sort | humoral response to plasmodium falciparum varo rosetting variant and its association with protection against malaria in beninese children |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2959068/ https://www.ncbi.nlm.nih.gov/pubmed/20923548 http://dx.doi.org/10.1186/1475-2875-9-267 |
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