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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Genetic diversity of VAR2CSA ID1-DBL2Xb in worldwide Plasmodium falciparum populations: Impact on vaccine design for placental malaria
Infection, Genetics and Evolution, Volume 25, Year 2014
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Description
In placental malaria (PM), sequestration of infected erythrocytes in the placenta is mediated by an interaction between VAR2CSA, a Plasmodium falciparum protein expressed on erythrocytes, and chondroitin sulfate A (CSA) on syncytiotrophoblasts. Recent works have identified ID1-DBL2Xb as the minimal CSA-binding region within VAR2CSA able to induce strong protective immunity, making it the leading candidate for the development of a vaccine against PM. Assessing the existence of population differences in the distribution of ID1-DBL2Xb polymorphisms is of paramount importance to determine whether geographic diversity must be considered when designing a candidate vaccine based on this fragment. In this study, we examined patterns of sequence variation of ID1-DBL2Xb in a large collection of P. falciparum field isolates (n= 247) from different malaria-endemic areas, including Africa (Benin, Senegal, Cameroon and Madagascar), Asia (Cambodia), Oceania (Papua New Guinea), and Latin America (Peru). Detection of variants and estimation of their allele frequencies were performed using next-generation sequencing of DNA pools. A considerable amount of variation was detected along the whole gene segment, suggesting that several allelic variants may need to be included in a candidate vaccine to achieve broad population coverage. However, most sequence variants were common and extensively shared among worldwide parasite populations, demonstrating long term persistence of those polymorphisms, probably maintained through balancing selection. Therefore, a vaccine mixture including such stable antigen variants will be putatively applicable and efficacious in all world regions where malaria occurs. Despite similarity in ID1-DBL2Xb allele repertoire across geographic areas, several peaks of strong population differentiation were observed at specific polymorphic loci, pointing out putative targets of humoral immunity subject to positive immune selection. © 2014 Elsevier B.V..
Authors & Co-Authors
Bordbar, Bita
France, Paris
Université Paris Cité
France, Marseille
Ird Institut de Recherche Pour le Developpement
Tuikue-Ndam, Nicaise
France, Paris
Université Paris Cité
France, Marseille
Ird Institut de Recherche Pour le Developpement
Benin, Cotonou
Centre D'etude et de Recherche Sur le Paludisme Associé à la Grossesse et à L'enfance Cerpage
Renard, Emmanuelle
France, Paris
Université Paris Cité
France, Marseille
Ird Institut de Recherche Pour le Developpement
Jafari-Guemouri, Sayeh
France, Paris
Université Paris Cité
France, Marseille
Ird Institut de Recherche Pour le Developpement
Tavul, Livingstone
Papua new Guinea, Goroka
Papua new Guinea Institute of Medical Research
Jennison, Charlie
Australia, Melbourne
Walter and Eliza Hall Institute of Medical Research
Gnidéhou, Sédami
France, Paris
Université Paris Cité
France, Marseille
Ird Institut de Recherche Pour le Developpement
Tahar, Rachida
France, Paris
Université Paris Cité
France, Marseille
Ird Institut de Recherche Pour le Developpement
Gamboa Vilela, Dionicia V.
Peru, Lima
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander Von Humboldt
Bendezú, Jorge
Peru, Lima
Universidad Peruana Cayetano Heredia, Instituto de Medicina Tropical Alexander Von Humboldt
Ménard, Didier
Cambodia, Phnom Penh
Institut Pasteur du Cambodge
Barry, Alyssa E.
Australia, Melbourne
Walter and Eliza Hall Institute of Medical Research
Deloron, Philippe
France, Paris
Université Paris Cité
France, Marseille
Ird Institut de Recherche Pour le Developpement
Sabbagh, Audrey
France, Paris
Université Paris Cité
France, Marseille
Ird Institut de Recherche Pour le Developpement
Statistics
Citations: 25
Authors: 14
Affiliations: 7
Identifiers
Doi:
10.1016/j.meegid.2014.04.010
ISSN:
15671348
e-ISSN:
15677257
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Study Design
Cross Sectional Study
Study Locations
Benin
Cameroon
Guinea
Madagascar
Senegal