@article{fdi:010062231, title = {{G}enetic diversity of {VAR}2{CSA} {ID}1-{DBL}2{X}b in worldwide {P}lasmodium falciparum populations : impact on vaccine design for placental malaria}, author = {{B}ordbar, {B}. and {T}uikue {N}dam, {N}icaise and {R}enard, {E}. and {G}uemouri, {S}ayeh and {T}avul, {L}. and {J}ennison, {C}. and {G}nidehou, {S}. and {T}ahar, {R}achida and {G}amboa, {D}. and {B}endezu, {J}. and {M}enard, {D}. and {B}arry, {A}. {E}. and {D}eloron, {P}hilippe and {S}abbagh, {A}.}, editor = {}, language = {{ENG}}, abstract = {{I}n placental malaria ({PM}), sequestration of infected erythrocytes in the placenta is mediated by an interaction between {VAR}2{CSA}, a {P}lasmodium falciparum protein expressed on erythrocytes, and chondroitin sulfate {A} ({CSA}) on syncytiotrophoblasts. {R}ecent works have identified {ID}1-{DBL}2{X}b as the minimal {CSA}-binding region within {VAR}2{CSA} able to induce strong protective immunity, making it the leading candidate for the development of a vaccine against {PM}. {A}ssessing the existence of population differences in the distribution of {ID}1-{DBL}2{X}b polymorphisms is of paramount importance to determine whether geographic diversity must be considered when designing a candidate vaccine based on this fragment. {I}n this study, we examined patterns of sequence variation of {ID}1-{DBL}2{X}b in a large collection of {P}. falciparum field isolates (n=247) from different malaria-endemic areas, including {A}frica ({B}enin, {S}enegal, {C}ameroon and {M}adagascar), {A}sia ({C}ambodia), {O}ceania ({P}apua {N}ew {G}uinea), and {L}atin {A}merica ({P}eru). {D}etection 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. {H}owever, most sequence variants were common and extensively shared among worldwide parasite populations, demonstrating long term persistence of those polymorphisms, probably maintained through balancing selection. {T}herefore, a vaccine mixture including such stable antigen variants will be putatively applicable and efficacious in all world regions where malaria occurs. {D}espite similarity in {ID}1-{DBL}2{X}b 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.}, keywords = {{P}regnancy-associated malaria ; {VAR}2{CSA} ; {P}lasmodium falciparum ; {V}accine ; {N}ext-generation sequencing ; {G}enetic structure ; {BENIN} ; {SENEGAL} ; {CAMEROUN} ; {MADAGASCAR} ; {CAMBODGE} ; {PAPOUASIE} {NOUVELLE} {GUINEE} ; {PEROU}}, booktitle = {}, journal = {{I}nfection {G}enetics and {E}volution}, volume = {25}, numero = {}, pages = {81--92}, ISSN = {1567-1348}, year = {2014}, DOI = {10.1016/j.meegid.2014.04.010}, URL = {https://www.documentation.ird.fr/hor/fdi:010062231}, }