@article{fdi:010091515, title = {{D}own-selection of the {VAR}2{CSA} {DBL}1-2 expressed in {E}. coli as a lead antigen for placental malaria vaccine development}, author = {{C}h{\^e}ne, {A}. and {G}angnard, {S}. and {D}echavanne, {C}{\'e}lia and {D}echavanne, {S}. and {S}rivastava, {A}. and {T}{\'e}tard, {M}. and {H}undt, {S}. and {L}eroy, {O}. and {H}avelange, {N}. and {V}iebig, {N}.{K}. and {G}amain, {B}.}, editor = {}, language = {{ENG}}, abstract = {{O}ver 50 million women are exposed to the risk of malaria during pregnancy every year. {M}alaria during pregnancy is a leading global cause of maternal morbidity and adverse pregnancy outcomes. {A}dhesion of {P}lasmodium falciparum-infected erythrocytes to placental chondroitin-4-sulfate ({CSA}) has been linked to the severe disease outcome of placental malaria. {A}ccumulated evidence strongly supports {VAR}2{CSA} as the leading placental malaria vaccine candidate. {R}ecombinant proteins encompassing the {VAR}2{CSA} high affinity {CSA} binding site have been generated, and their activity as immunogens that elicit functional (inhibitory) and cross-reactive antibodies against {CSA}-binding parasites assessed. {T}he expression of {H}is-tagged proteins was compared in four different expression systems and their capacity to bind specifically to {CSA} was analyzed. {CHO} cells and {E}. coli {SH}uffle cells were the two expression systems able to express some of the recombinant proteins in reasonable amounts. {L}arger analytical scale production of {DBL}1x-2× (3{D}7) and {DBL}3x-4? ({FCR}3) best expressed in {CHO} and {E}. coli {SH}uffle cells were performed. {P}urified proteins were administered to rats either alone or adjuvanted with human approved adjuvants. {A}nalysis of the functionality and cross-reactivity of the induced antibodies allowed us to down-select the {DBL}1x-2(3{D}7) expressed in {E}. coli {SH}uffle cells as the best antigen to be transitioned to further clinical development in order to protect future pregnant women living in malaria endemic areas against the severe clinical outcomes of placental malaria.}, keywords = {{AFRIQUE} {SUBSAHARIENNE}}, booktitle = {}, journal = {{NPJ} {V}accines}, volume = {3}, numero = {1}, pages = {28 [11 ]}, ISSN = {2059-0105}, year = {2018}, DOI = {10.1038/s41541-018-0064-6}, URL = {https://www.documentation.ird.fr/hor/fdi:010091515}, }