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Seroreactivity to Plasmodium falciparum erythrocyte membrane protein 1 intracellular domain in malaria-exposed children and adults.

ABSTRACT: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens mediate parasite sequestration and host immune evasion. Reactivity to 21 PfEMP1 fragments on a protein microarray was measured in serum samples from Malian children aged 1-6 years and adults. Seroreactivity to PfEMP1 fragments was higher in adults than in children; intracellular conserved fragments were more widely recognized than were extracellular hypervariable fragments. Over a malaria season, children maintained this differential seroreactivity and recognized additional intracellular PfEMP1 fragments. This approach has the potential to identify conserved, seroreactive extracellular PfEMP1 domains critical for protective immunity to malaria.

SUBMITTER: Travassos MA

PROVIDER: S-EPMC3789569 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Seroreactivity to Plasmodium falciparum erythrocyte membrane protein 1 intracellular domain in malaria-exposed children and adults.

Travassos Mark A MA Niangaly Amadou A Bailey Jason A JA Ouattara Amed A Coulibaly Drissa D Laurens Matthew B MB Pablo Jozelyn J Jasinskas Algis A Nakajima-Sasaki Rie R Berry Andrea A AA Takala-Harrison Shannon S Kouriba Bourema B Rowe J Alexandra JA Lyke Kirsten E KE Doumbo Ogobara K OK Thera Mahamadou A MA Felgner Philip L PL Plowe Christopher V CV

The Journal of infectious diseases 20130730 9

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) antigens mediate parasite sequestration and host immune evasion. Reactivity to 21 PfEMP1 fragments on a protein microarray was measured in serum samples from Malian children aged 1-6 years and adults. Seroreactivity to PfEMP1 fragments was higher in adults than in children; intracellular conserved fragments were more widely recognized than were extracellular hypervariable fragments. Over a malaria season, children maintained this diff ...[more]

PMID: 23901079

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Project description:BACKGROUND:Antibody immunity is thought to be essential to prevent severe Plasmodium falciparum infection, but the exact correlates of protection are unknown. Over time, children in endemic areas acquire non-sterile immunity to malaria that correlates with development of antibodies to merozoite invasion proteins and parasite proteins expressed on the surface of infected erythrocytes. RESULTS:A 1000 feature P. falciparum 3D7 protein microarray was used to compare P. falciparum-specific seroreactivity during acute infection and 30 days after infection in 23 children with uncomplicated malaria (UM) and 25 children with retinopathy-positive cerebral malaria (CM). All children had broad P. falciparum antibody reactivity during acute disease. IgM reactivity decreased and IgG reactivity increased in convalescence. Antibody reactivity to CIDR domains of "virulent" PfEMP1 proteins was low with robust reactivity to the highly conserved, intracellular ATS domain of PfEMP1 in both groups. Although children with UM and CM differed markedly in parasite burden and PfEMP1 exposure during acute disease, neither acute nor convalescent PfEMP1 seroreactivity differed between groups. Greater seroprevalence to a conserved Group A-associated ICAM binding extracellular domain was observed relative to linked extracellular CIDRα1 domains in both case groups. Pooled immune IgG from Malawian adults revealed greater reactivity to PfEMP1 than observed in children. CONCLUSIONS:Children with uncomplicated and cerebral malaria have similar breadth and magnitude of P. falciparum antibody reactivity. The utility of protein microarrays to measure serological recognition of polymorphic PfEMP1 antigens needs to be studied further, but the study findings support the hypothesis that conserved domains of PfEMP1 are more prominent targets of cross reactive antibodies than variable domains in children with symptomatic malaria. Protein microarrays represent an additional tool to identify cross-reactive Plasmodium antigens including PfEMP1 domains that can be investigated as strain-transcendent vaccine candidates.

Dataset Information

Seroreactivity to Plasmodium falciparum erythrocyte membrane protein 1 intracellular domain in malaria-exposed children and adults.

Publications

Seroreactivity to Plasmodium falciparum erythrocyte membrane protein 1 intracellular domain in malaria-exposed children and adults.

Similar Datasets

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