@article{fdi:010042646,
  title = {{I}dentification of glycosaminoglycan binding regions in the {P}lasmodium falciparum encoded placental sequestration ligand, {VAR}2{CSA} - art. no. 104},
  author = {{R}esende, {M}. and {N}ielsen, {M}. {A}. and {D}ahlbaeck, {M}. and {D}itlev, {S}. {B}. and {A}ndersen, {P}. and {S}ander, {A}. {F}. and {T}uikue {N}dam, {N}icaise and {T}heander, {T}. {G}. and {S}alanti, {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {P}regnancy malaria is caused by {P}lasmodium falciparum-infected erythrocytes binding the placental receptor chondroitin sulfate {A} ({CSA}). {T}his results in accumulation of parasites in the placenta with severe clinical consequences for the mother and her unborn child. {W}omen become resistant to placental malaria as antibodies are acquired which specifically target the surface of infected erythrocytes binding in the placenta. {VAR}2{CSA} is most likely the parasite-encoded protein which mediates binding to the placental receptor {CSA}. {S}everal domains have been shown to bind {CSA} in vitro; and it is apparent that a {VAR}2{CSA}-based vaccine cannot accommodate all the {CSA} binding domains and serovariants. {I}t is thus of high priority to define minimal ligand binding regions throughout the {VAR}2{CSA} molecule. {M}ethods: {T}o define minimal {CSA}-binding regions/peptides of {VAR}2{CSA}, a phage display library based on the entire var2csa coding region was constructed. {T}his library was screened on immobilized {CSA} and cells expressing {CSA} resulting in a limited number of {CSA}-binding phages. {A}ntibodies against these peptides were affinity purified and tested for reactivity against {CSA}-binding infected erythrocytes. {R}esults: {T}he most frequently identified phages expressed peptides residing in the parts of {VAR}2{CSA} previously defined as {CSA} binding. {I}n addition, most of the binding regions mapped to surface-exposed parts of {VAR}2{CSA}. {T}he binding of a {DBL}2{X} peptide to {CSA} was confirmed with a synthetic peptide. {A}ntibodies against a {CSA}-binding {DBL}2{X} peptide reacted with the surface of infected erythrocytes indicating that this epitope is accessible for antibodies on native {VAR}2{CSA} on infected erythrocytes. {C}onclusion: {S}hort continuous regions of {VAR}2{CSA} with affinity for multiple types of {CSA} were defined. {A} number of these regions localize to {CSA}-binding domains and to surface-exposed regions within these domains and a synthetic peptide corresponding to a peptide sequence in {DBL}2 was shown to bind to {CSA} and not to {CSC}. {I}t is likely that some of these epitopes are involved in native parasite {CSA} adhesion. {H}owever, antibodies directed against single epitopes did not inhibit parasite adhesion. {T}his study supports phage display as a technique to identify {CSA}-binding regions of large proteins such as {VAR}2{CSA}.},
  keywords = {},
  booktitle = {},
  journal = {{M}alaria {J}ournal},
  volume = {7},
  numero = {104},
  pages = {6},
  ISSN = {1475-2875},
  year = {2008},
  DOI = {10.1186/1475-2875-7-104},
  URL = {https://www.documentation.ird.fr/hor/fdi:010042646},
}