Universidad Peruana Cayetano Heredia

Genetic diversity of VAR2CSA ID1-DBL2Xb in worldwide Plasmodium falciparum populations: impact on vaccine design for placental malaria

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dc.contributor.author Bordbar, Bita
dc.contributor.author Tuikue Ndam, Nicaise
dc.contributor.author Renard, Emmanuelle
dc.contributor.author Jafari-Guemouri, Sayeh
dc.contributor.author Tavul, Livingstone
dc.contributor.author Jennison, Charlie
dc.contributor.author Gnidehou, Sedami
dc.contributor.author Tahar, Rachida
dc.contributor.author Gamboa Vilela, Dionicia Baziliza
dc.contributor.author Bendezu, Jorge
dc.contributor.author Menard, Didier
dc.contributor.author Barry, Alyssa E.
dc.contributor.author Deloron, Philippe
dc.contributor.author Sabbagh, Audrey
dc.date.accessioned 2020-06-10T18:11:30Z
dc.date.available 2020-06-10T18:11:30Z
dc.date.issued 2014
dc.identifier.uri https://hdl.handle.net/20.500.12866/7963
dc.description.abstract 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. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartofseries Infection, Genetics and Evolution
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Adolescent en_US
dc.subject Adult en_US
dc.subject Antigenic Variation/immunology en_US
dc.subject Antigens, Protozoan/genetics/immunology en_US
dc.subject DNA, Protozoan/genetics en_US
dc.subject Female en_US
dc.subject Gene Frequency en_US
dc.subject Genetic structure en_US
dc.subject Genetic Variation en_US
dc.subject Humans en_US
dc.subject Malaria, Falciparum/epidemiology/immunology/parasitology en_US
dc.subject Next-generation sequencing en_US
dc.subject Phylogeography en_US
dc.subject Placenta/immunology/parasitology en_US
dc.subject Plasmodium falciparum en_US
dc.subject Plasmodium falciparum/classification/immunology/isolation & purification/metabolism en_US
dc.subject Pregnancy en_US
dc.subject Pregnancy Complications, Parasitic/immunology/parasitology en_US
dc.subject Pregnancy-associated malaria en_US
dc.subject Sequence Analysis, DNA en_US
dc.subject Vaccine en_US
dc.subject VAR2CSA en_US
dc.subject Viral Vaccines/genetics/immunology en_US
dc.subject Young Adult en_US
dc.title Genetic diversity of VAR2CSA ID1-DBL2Xb in worldwide Plasmodium falciparum populations: impact on vaccine design for placental malaria en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1016/j.meegid.2014.04.010
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.07
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.relation.issn 1567-7257


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