@article{PAR00005959,
  title = {{T}owards the rational design of a candidate vaccine against pregnancy associated malaria : conserved sequences of the {DBL}6 epsilon domain of {VAR}2{CSA}},
  author = {{B}adaut, {C}yril and {B}ertin, {G}wladys and {R}ustico, {T}atiana and {F}ievet, {N}adine and {M}assougbodji, {A}. and {G}aye, {A}. and {D}eloron, {P}hilippe},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {P}lacental malaria is a disease linked to the sequestration of {P}lasmodium falciparum infected red blood cells ({IRBC}) in the placenta, leading to reduced materno-fetal exchanges and to local inflammation. {O}ne of the virulence factors of {P}. falciparum involved in cytoadherence to chondroitin sulfate {A}, its placental receptor, is the adhesive protein {VAR}2{CSA}. {I}ts localisation on the surface of {IRBC} makes it accessible to the immune system. {VAR}2{CSA} contains six {DBL} domains. {T}he {DBL}6 epsilon domain is the most variable. {H}igh variability constitutes a means for the parasite to evade the host immune response. {T}he {DBL}6 epsilon domain could constitute a very attractive basis for a vaccine candidate but its reported variability necessitates, for antigenic characterisations, identifying and classifying commonalities across isolates. {M}ethodology/{P}rincipal {F}indings: {L}ocal alignment analysis of the {DBL}6 epsilon domain had revealed that it is not as variable as previously described. {V}ariability is concentrated in seven regions present on the surface of the {DBL}6 epsilon domain. {T}he main goal of our work is to classify and group variable sequences that will simplify further research to determine dominant epitopes. {F}irstly, variable sequences were grouped following their average percent pairwise identity ({APPI}). {G}roups comprising many variable sequences sharing low variability were found. {S}econdly, {ELISA} experiments following the {I}g{G} recognition of a recombinant {DBL}6 epsilon domain, and of peptides mimicking its seven variable blocks, allowed to determine an {APPI} cut-off and to isolate groups represented by a single consensus sequence. {C}onclusions/{S}ignificance: {A} new sequence approach is used to compare variable regions in sequences that have extensive segmental gene relationship. {U}sing this approach, the {VAR}2{CSA} {DBL}6 domain is composed of 7 variable blocks with limited polymorphism. {E}ach variable block is composed of a limited number of consensus types. {B}ased on peptide based {ELISA}, variable blocks with 85% or greater sequence identity are expected to be recognized equally well by antibody and can be considered the same consensus type. {T}herefore, the analysis of the antibody response against the classified small number of sequences should be helpful to determine epitopes.},
  keywords = {},
  booktitle = {},
  journal = {{P}los {O}ne},
  volume = {5},
  numero = {6},
  pages = {e11276},
  ISSN = {1932-6203},
  year = {2010},
  DOI = {10.1371/journal.pone.0011276},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00005959},
}