@article{fdi:010055710,
  title = {{I}dentification of {I}d1-{DBL}2{X} of {VAR}2{CSA} as a key domain inducing highly inhibitory and cross-reactive antibodies},
  author = {{B}ordbar, {B}ita and {T}uikue {N}dam, {N}icaise and {B}igey, {P}. and {D}oritchamou, {J}. and {S}cherman, {D}. and {D}eloron, {P}hilippe},
  editor = {},
  language = {{ENG}},
  abstract = {{P}urpose of the research: {VAR}2{CSA} is considered as the main target of protective immunity against pregnancy-associated malaria. {VAR}2{CSA} high molecular weight complicates scaling up production of {VAR}2{CSA} recombinant protein for large-scale vaccination programmes. {W}e previously demonstrated that antibodies induced by {NTS}-{DBL}1{X}-{I}d1-{DBL}2{X} efficiently block parasite binding to {CSA} in a similar manner to antibodies induced by the full-length extracellular part of {VAR}2{CSA}. {I}n order to identifying the shortest fragment of {VAR}2{CSA} carrying major protective epitopes able to elicit inhibitory antibodies, we performed a refined antigenic mapping of {NTS}-{DBL}1{X}-{I}d1-{DBL}2{X} through a {DNA} vaccination technique. {P}rincipal results: {F}ive single or double domains constructs encoding {NTS}-{DBL}1{X}, {NTS}-{DBL}1{X}-{I}d1, {I}d1, {I}d1-{DBL}2{X} and {DBL}2{X} were made and used to immunize mice. {T}he {NTS}-{DBL}1{X}, {NTS}-{DBL}1{X}-{I}d1, and {I}d1-{DBL}2{X} fragments all raised high titer immune response, as measured by {ELISA}. {T}he {DBL}2{X} fragment raised a weaker antibody titer, and the {I}d1 construct failed to elicit antibody. {S}era from mice immunized with {NTS}-{DBL}1{X} or {DBL}2{X} constructs failed to block infected erythrocytes binding to {CSA}, whereas sera from mice immunized with {NTS}-{DBL}1{X}-{I}d1 showed partial inhibitory activity, and the {I}d1-{DBL}2{X} fragment elicited antisera that totally abrogated infected erythrocytes adhesion to {CSA}. {I}g{G} purified from {I}d1-{DBL}2{X} antisera showed a similar inhibitory profile than {I}d1-{DBL}2{X} antisera. {A}nti-{FCR}3 anti-{I}d1-{DBL}2{X} antibodies also efficiently block the adhesion of erythrocytes infected by the {HB}3 parasite line to {CSA}. {I}d1-{DBL}2{X} antisera recognized the surface of field isolates from pregnant women, and inhibited {CSA}-binding of all 8 isolates tested, although to a variable level. {M}ajor conclusions: {W}e raised high-titer antibodies against several parts of the protein, and identified {I}d1-{DBL}2{X} as the minimal {VAR}2{CSA} fragment inducing antibodies with {CSA}-binding inhibitory efficiency in the same range as the full-length extracellular part of {VAR}2{CSA}.},
  keywords = {{VAR}2{CSA} ; {V}accine ; {M}alaria ; {P}lasmodium falciparum ; {P}lacenta ; {P}regnancy},
  booktitle = {},
  journal = {{V}accine},
  volume = {30},
  numero = {7},
  pages = {1343--1348},
  ISSN = {0264-410{X}},
  year = {2012},
  DOI = {10.1016/j.vaccine.2011.12.065},
  URL = {https://www.documentation.ird.fr/hor/fdi:010055710},
}