@article{PAR00013356, title = {{P}arity-dependent recognition of {DBL}1{X}-3{X} suggests an important role of the {VAR}2{CSA} high-affinity {CSA}-binding region in the development of the humoral response against placental malaria}, author = {{D}echavanne, {S}. and {S}rivastava, {A}. and {G}angnard, {S}. and {N}unes-{S}ilva, {S}. and {D}echavanne, {C}. and {F}ievet, {N}adine and {D}eloron, {P}hilippe and {C}hene, {A}. and {G}amain, {B}.}, editor = {}, language = {{ENG}}, abstract = {{P}lasmodium falciparum multidomain protein {VAR}2{CSA} stands today as the leading vaccine candidate against pregnancy-associated malaria ({PAM}). {M}ost of the studies aiming to decrypt how naturally acquired immunity develops have assessed the immune recognition of individual {VAR}2{CSA} {D}uffy-binding-like ({DBL}) domains, thus overlooking the presence of conformational epitopes resulting from the overall folding of the full-length protein. {I}n order to characterize the development of humoral immunity toward {VAR}2{CSA}, we made use of a large cohort of 293 {S}enegalese pregnant women to assess the level of recognition by plasma {I}g{G} of the full-length {VAR}2{CSA} protein of the 3{D}7 parasite strain (3{D}7-{VAR}2{CSA}), the {CSA}-binding multidomains 3{D}7-{DBL}1{X} to -{DBL}3{X} (3{D}7-{DBL}1{X}-3{X}), and the {CSA} nonbinding multidomains 3{D}7-{DBL}4 epsilon to -{DBL}6 epsilon (3{D}7-{DBL}4 epsilon-6 epsilon), as well as individual 3{D}7-{DBL} domains. {O}ur results revealed a parity-dependent recognition of the full-length 3{D}7-{VAR}2{CSA} and of the {CSA}-binding region, 3{D}7-{DBL}1{X}-3{X}. {I}ndeed, multigravid women possess significantly higher levels of antibodies directed against these constructs than primigravidae. {O}ur results suggest an important role of antibodies targeting the {CSA}-binding region in the development of immunity against {PAM}, therefore providing new insights on how natural protection might be acquired and further information for the design of {VAR}2{CSA}-based vaccines.}, keywords = {}, booktitle = {}, journal = {{I}nfection and {I}mmunity}, volume = {83}, numero = {6}, pages = {2466--2474}, ISSN = {0019-9567}, year = {2015}, DOI = {10.1128/iai.03116-14}, URL = {https://www.documentation.ird.fr/hor/{PAR}00013356}, }