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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...

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Autores principales: Vigan-Womas, Inès, Lokossou, Adjimon, Guillotte, Micheline, Juillerat, Alexandre, Bentley, Graham, Garcia, André, Mercereau-Puijalon, Odile, Migot-Nabias, Florence
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
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.
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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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