@article{fdi:010052847,
  title = {{I}nsight into antigenic diversity of {VAR}2{CSA}-{DBL}5 epsilon domain from multiple {P}lasmodium falciparum placental isolates},
  author = {{G}nidehou, {S}{\'e}dami and {J}essen, {L}. and {G}angnard, {S}. and {E}rmont, {C}aroline and {T}riqui, {C}houkri and {Q}uiviger, {M}icka{\¨e}l and {G}uitard, {J}uliette and {L}und, {O}. and {D}eloron, {P}hilippe and {T}uikue {N}dam, {N}icaise},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {P}rotection against pregnancy associated malaria ({PAM}) is associated with high levels of anti-{VAR}2{CSA} antibodies. {T}his protection is obtained by the parity dependent acquisition of anti-{VAR}2{CSA} antibodies. {D}istinct parity-associated molecular signatures have been identified in {VAR}2{CSA} domains. {T}hese two observations combined point to the importance of identifying {VAR}2{CSA} sequence variation, which facilitate parasitic evasion or subversion of host immune response. {H}ighly conserved domains of {VAR}2{CSA} such as {DBL}5e are likely to contain conserved epitopes, and therefore do constitute attractive targets for vaccine development. {M}ethodology/{P}rincipal {F}indings: {VAR}2{CSA} {DBL}5e-domain sequences obtained from c{DNA} of 40 placental isolates were analysed by a combination of experimental and in silico methods. {C}ompetition {ELISA} assays on two {DBL}5e variants, using plasma samples from women from two different areas and specific mice hyperimmune plasma, indicated that {DBL}5e possess conserved and cross-reactive {B} cell epitopes. {P}eptide {ELISA} identified conserved areas that are recognised by naturally acquired antibodies. {S}pecific antibodies against these peptides labelled the native proteins on the surface of placental parasites. {D}espite high {DBL}5e sequence homology among parasite isolates, sequence analyses identified motifs in {DBL}5e that discriminate parasites according to donor's parity. {M}oreover, recombinant proteins of two {VAR}2{CSA} {DBL}5e variants displayed diverse recognition patterns by plasma from malaria-exposed women, and diverse proteoglycan binding abilities. {C}onclusions/{S}ignificance: {T}his study provides insights into conserved and exposed {B} cell epitopes in {DBL}5e that might be a focus for cross reactivity. {T}he importance of sequence variation in {VAR}2{CSA} as a critical challenge for vaccine development is highlighted. {VAR}2{CSA} conformation seems to be essential to its functionality. {T}herefore, identification of sequence variation sites in distinct locations within {VAR}2{CSA}, affecting antigenicity and/or binding properties, is critical to the effort of developing an efficient {VAR}2{CSA}-based vaccine. {M}otifs associated with parasite segregation according to parity constitute one such site.},
  keywords = {},
  booktitle = {},
  journal = {{P}los {O}ne},
  volume = {5},
  numero = {10},
  pages = {e13105},
  ISSN = {1932-6203},
  year = {2010},
  DOI = {10.1371/journal.pone.0013105},
  URL = {https://www.documentation.ird.fr/hor/fdi:010052847},
}