Lack of Gender-Specific Antibody Recognition of Products from Domains of a
            <i>var</i>
            Gene Implicated in Pregnancy-Associated
            <i>Plasmodium falciparum</i>
            Malaria

Jensen, Anja T. R.; Zornig, Hanne D.; Buhmann, Caecilie; Salanti, Ali; Koram, Kwadwo A.; Riley, Eleanor M.; Theander, Thor G.; Hviid, Lars; Staalsøe, Trine

doi:10.1128/iai.71.7.4193-4196.2003

Cited by 20 publications

(18 citation statements)

References 27 publications

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“…Blocking of the plasma pool was done with 4 g/ml recombinant protein (x: recombinant proteins 1 to 60) for 2 h at room temperature. The preabsorbed pool was diluted 1:100, and 100 l was added to duplicate wells of Maxisorp microtiter plates precoated with antigen (1 to 5 g/ml) or GST as a control antigen (14). In addition to the preabsorbed pool (pPx), a nonabsorbed pool (nP) was included in each plate.…”

Section: Methodsmentioning

confidence: 99%

Limited Cross-Reactivity among Domains of the Plasmodium falciparum Clone 3D7 Erythrocyte Membrane Protein 1 Family

et al. 2006

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The var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family is responsible for antigenic variation and sequestration of infected erythrocytes during malaria. We have previously grouped the 60 PfEMP1 variants of P. falciparum clone 3D7 into groups A and B/A (category A) and groups B, B/C, and C (category non-A). Expression of category A molecules is associated with severe malaria, and that of category non-A molecules is associated with uncomplicated malaria and asymptomatic infection. Here we assessed cross-reactivity among 60 different recombinant PfEMP1 domains derived from clone 3D7 by using a competition enzyme-linked immunosorbent assay and a pool of plasma from 63 malaria-exposed Tanzanian individuals. We conclude that naturally acquired antibodies are largely directed toward epitopes varying between different domains with a few, mainly category A, domains sharing cross-reactive antibody epitopes. Identification of groups of serological cross-reacting molecules is pivotal for the development of vaccines based on PfEMP1.

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Section: Methodsmentioning

confidence: 99%

Limited Cross-Reactivity among Domains of the Plasmodium falciparum Clone 3D7 Erythrocyte Membrane Protein 1 Family

et al. 2006

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“…Dilutions (1:100) of plasma samples were incubated in 96-well MaxiSorp plates (Nunc, Denmark) precoated with recombinant PF11_0008 domains at a concentration of 1 or 2 g/ml (depending on the point of signal saturation using antihistidine antibodies) in 100 l coating buffer (0.1 M glycine HCl, pH 2.75) and processed as described previously (22). Antibody responses were expressed in arbitrary units calculated as follows: (optical density of sample Ϫ optical density of background)/(optical density of positive control sample Ϫ optical density of background).…”

Section: Methodsmentioning

confidence: 99%

Immunoglobulin G Antibody Reactivity to a Group A Plasmodium falciparum Erythrocyte Membrane Protein 1 and Protection from P. falciparum Malaria

et al. 2007

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Variant surface antigens (VSA) on the surface of Plasmodium falciparum-infected red blood cells play a major role in the pathogenesis of malaria and are key targets for acquired immunity. The best-characterized VSA belong to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. In areas where P. falciparum is endemic, parasites causing severe malaria and malaria in young children with limited immunity tend to express semiconserved PfEMP1 molecules encoded by group A var genes. Here we investigated antibody responses of Tanzanians who were 0 to 19 years old to PF11_0008, a group A PfEMP1. PF11_0008 has previously been found to be highly transcribed in a nonimmune Dutch volunteer experimentally infected with NF54 parasites. A high proportion of the Tanzanian donors had antibodies against recombinant PF11_0008 domains, and in children who were 4 to 9 years old the presence of antibodies to the PF11_0008 CIDR2␤ domain was associated with reduced numbers of malaria episodes. These results indicate that homologues of PF11_0008 are present in P. falciparum field isolates and suggest that PF11_0008 CIDR2␤-reactive antibodies might be involved in protection against malaria episodes.

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“…However, other studies suggest that var1csa is not central to adhesion of placental parasites. Transcription of var1csa is not restricted to placental parasites (19), and seroreactivity to expressed VAR1CSA is not parity related (31,50). After selection on CSA, the FCR3 knockout parasite regained binding to CSA and expressed a novel PfEMP1 gene, subsequently shown to be var2csa (3,23).…”

mentioning

confidence: 97%

Six Genes Are Preferentially Transcribed by the Circulating and Sequestered Forms of Plasmodium falciparum Parasites That Infect Pregnant Women

et al. 2007

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In areas of stable malaria transmission, susceptibility to Plasmodium falciparum malaria increases during first pregnancy. Women become resistant to pregnancy malaria over successive pregnancies as they acquire antibodies against the parasite forms that sequester in the placenta, suggesting that a vaccine is feasible. Placental parasites are antigenically distinct and bind receptors, like chondroitin sulfate A (CSA), that are not commonly bound by other parasites. We used whole-genome-expression analysis to find transcripts that distinguish parasites of pregnant women from other parasites and employed a novel approach to define and adjust for cell cycle timing of parasites. Transcription of six genes was substantially higher in both placental parasites and peripheral parasites from pregnant women, and each gene encodes a protein with a putative export sequence and/or transmembrane domain. This cohort of genes includes var2csa, a member of the variant PfEMP1 gene family previously implicated in pregnancy malaria, as well as five conserved genes of unknown functions. Women in East Africa acquire antibodies over successive pregnancies against a protein encoded by one of these genes, PFD1140w, and this protein shows seroreactivity similar to that of VAR2CSA domains. These findings suggest that a suite of genes may be important for the genesis of the placental binding phenotype of P. falciparum and may provide novel targets for therapeutic intervention.

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Lack of Gender-Specific Antibody Recognition of Products from Domains of a var Gene Implicated in Pregnancy-Associated Plasmodium falciparum Malaria

Cited by 20 publications

References 27 publications

Limited Cross-Reactivity among Domains of the Plasmodium falciparum Clone 3D7 Erythrocyte Membrane Protein 1 Family

Limited Cross-Reactivity among Domains of the Plasmodium falciparum Clone 3D7 Erythrocyte Membrane Protein 1 Family

Immunoglobulin G Antibody Reactivity to a Group A Plasmodium falciparum Erythrocyte Membrane Protein 1 and Protection from P. falciparum Malaria

Six Genes Are Preferentially Transcribed by the Circulating and Sequestered Forms of Plasmodium falciparum Parasites That Infect Pregnant Women

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