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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Induction of strain-transcending antibodies against group A PfEMP1 surface antigens from virulent malaria parasites
PLoS Pathogens, Volume 8, No. 4, Article e1002665, Year 2012
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Description
Sequence diversity in pathogen antigens is an obstacle to the development of interventions against many infectious diseases. In malaria caused by Plasmodium falciparum, the PfEMP1 family of variant surface antigens encoded by var genes are adhesion molecules that play a pivotal role in malaria pathogenesis and clinical disease. PfEMP1 is a major target of protective immunity, however, development of drugs or vaccines based on PfEMP1 is problematic due to extensive sequence diversity within the PfEMP1 family. Here we identified the PfEMP1 variants transcribed by P. falciparum strains selected for a virulence-associated adhesion phenotype (IgM-positive rosetting). The parasites transcribed a subset of Group A PfEMP1 variants characterised by an unusual PfEMP1 architecture and a distinct N-terminal domain (either DBLα1.5 or DBLα1.8 type). Antibodies raised in rabbits against the N-terminal domains showed functional activity (surface reactivity with live infected erythrocytes (IEs), rosette inhibition and induction of phagocytosis of IEs) down to low concentrations (<10 μg/ml of total IgG) against homologous parasites. Furthermore, the antibodies showed broad cross-reactivity against heterologous parasite strains with the same rosetting phenotype, including clinical isolates from four sub-Saharan African countries that showed surface reactivity with either DBLα1.5 antibodies (variant HB3var6) or DBLα1.8 antibodies (variant TM284var1). These data show that parasites with a virulence-associated adhesion phenotype share IE surface epitopes that can be targeted by strain-transcending antibodies to PfEMP1. The existence of shared surface epitopes amongst functionally similar disease-associated P. falciparum parasite isolates suggests that development of therapeutic interventions to prevent severe malaria is a realistic goal. © 2012 Ghumra et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s001.tif
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https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s003.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s004.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s005.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s006.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s007.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s008.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s009.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s010.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s011.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s012.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s013.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s014.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s015.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s016.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3330128/bin/ppat.1002665.s017.doc
Authors & Co-Authors
Ghumra, Ashfaq
United Kingdom, Edinburgh
The University of Edinburgh
Semblat, Jean Philippe
United Kingdom, Edinburgh
The University of Edinburgh
Ataíde, Ricardo
United Kingdom, Edinburgh
The University of Edinburgh
Kifude, Carolyne M.
United Kingdom, Edinburgh
The University of Edinburgh
Kenya, Nairobi
Kenya Medical Research Institute
Adams, Yvonne
United Kingdom, Edinburgh
The University of Edinburgh
Claessens, Antoine
United Kingdom, Edinburgh
The University of Edinburgh
Anong, Damian Nota
Cameroon, Buea
University of Buea
Bull, Peter C.
Kenya, Nairobi
Kenya Medical Research Institute
Fennell, Clare
United Kingdom, Edinburgh
The University of Edinburgh
Arman, Mònica
United Kingdom, Edinburgh
The University of Edinburgh
Amambua-Ngwa, Alfred
Gambia, Banjul
Medical Research Council Laboratories Gambia
Walther, Michael
Gambia, Banjul
Medical Research Council Laboratories Gambia
Conway, David J.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Kassambara, L.
Mali, Bamako
University of Bamako
Doumbo, Ogobara K.
Mali, Bamako
University of Bamako
Raza, Ahmed J.
United Kingdom, Edinburgh
The University of Edinburgh
Rowe, Jane Alexandra
United Kingdom, Edinburgh
The University of Edinburgh
Statistics
Citations: 78
Authors: 17
Affiliations: 5
Identifiers
Doi:
10.1371/journal.ppat.1002665
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Infectious Diseases