%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Bordbar, Bita
%A Tuikue Ndam, Nicaise
%A Bigey, P.
%A Doritchamou, J.
%A Scherman, D.
%A Deloron, Philippe
%T Identification of Id1-DBL2X of VAR2CSA as a key domain inducing highly inhibitory and cross-reactive antibodies
%D 2012
%L fdi:010055710
%G ENG
%J Vaccine
%@ 0264-410X
%K VAR2CSA ; Vaccine ; Malaria ; Plasmodium falciparum ; Placenta ; Pregnancy
%M ISI:000301565900015
%N 7
%P 1343-1348
%R 10.1016/j.vaccine.2011.12.065
%U https://www.documentation.ird.fr/hor/fdi:010055710
%> https://www.documentation.ird.fr/intranet/publi/2012/04/010055710.pdf
%V 30
%W Horizon (IRD)
%X Purpose of the research: VAR2CSA is considered as the main target of protective immunity against pregnancy-associated malaria. VAR2CSA high molecular weight complicates scaling up production of VAR2CSA recombinant protein for large-scale vaccination programmes. We previously demonstrated that antibodies induced by NTS-DBL1X-Id1-DBL2X efficiently block parasite binding to CSA in a similar manner to antibodies induced by the full-length extracellular part of VAR2CSA. In order to identifying the shortest fragment of VAR2CSA carrying major protective epitopes able to elicit inhibitory antibodies, we performed a refined antigenic mapping of NTS-DBL1X-Id1-DBL2X through a DNA vaccination technique. Principal results: Five single or double domains constructs encoding NTS-DBL1X, NTS-DBL1X-Id1, Id1, Id1-DBL2X and DBL2X were made and used to immunize mice. The NTS-DBL1X, NTS-DBL1X-Id1, and Id1-DBL2X fragments all raised high titer immune response, as measured by ELISA. The DBL2X fragment raised a weaker antibody titer, and the Id1 construct failed to elicit antibody. Sera from mice immunized with NTS-DBL1X or DBL2X constructs failed to block infected erythrocytes binding to CSA, whereas sera from mice immunized with NTS-DBL1X-Id1 showed partial inhibitory activity, and the Id1-DBL2X fragment elicited antisera that totally abrogated infected erythrocytes adhesion to CSA. IgG purified from Id1-DBL2X antisera showed a similar inhibitory profile than Id1-DBL2X antisera. Anti-FCR3 anti-Id1-DBL2X antibodies also efficiently block the adhesion of erythrocytes infected by the HB3 parasite line to CSA. Id1-DBL2X antisera recognized the surface of field isolates from pregnant women, and inhibited CSA-binding of all 8 isolates tested, although to a variable level. Major conclusions: We raised high-titer antibodies against several parts of the protein, and identified Id1-DBL2X as the minimal VAR2CSA fragment inducing antibodies with CSA-binding inhibitory efficiency in the same range as the full-length extracellular part of VAR2CSA.
%$ 052