@article{fdi:010065258,
  title = {{T}he influence of sub-unit composition and expression system on the functional antibody response in the development of a {VAR}2{CSA} based {P}lasmodium falciparum placental malaria vaccine},
  author = {{N}ielsen, {M}. {A}. and {R}esende, {M}. and de {J}ongh, {W}. {A}. and {D}itlev, {S}. {B}. and {M}ordmuller, {B}. and {H}ouard, {S}. and {T}uikue {N}dam, {N}icaise and {A}gerbaek, {M}. {O}. and {H}amborg, {M}. and {M}assougbodji, {A}. and {I}ssifou, {S}. and {S}trobaek, {A}. and {P}oulsen, {L}. and {L}eroy, {O}. and {K}remsner, {P}. {G}. and {C}hippaux, {J}ean-{P}hilippe and {L}uty, {A}drian and {D}eloron, {P}hilippe and {T}heander, {T}. {G}. and {D}yring, {C}. and {S}alanti, {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{T}he disease caused by {P}lasmodium falciparum ({P}f) involves different clinical manifestations that, cumulatively, kill hundreds of thousands every year. {P}lacental malaria ({PM}) is one such manifestation in which {P}f infected erythrocytes ({IE}) bind to chondroitin sulphate {A} ({CSA}) through expression of {VAR}2{CSA}, a parasite-derived antigen. {P}rotection against {PM} is mediated by antibodies that inhibit binding of {IE} in the placental intervillous space. {VAR}2{CSA} is a large antigen incompatible with large scale recombinant protein expression. {V}accines based on sub-units encompassing the functionally constrained receptor-binding domains may, theoretically, circumvent polymorphisms, reduce the risk of escape-mutants and induce cross-reactive antibodies. {H}owever, the sub-unit composition and small differences in the borders, may lead to exposure of novel immuno-dominant antibody epitopes that lead to non-functional antibodies, and furthermore influence the folding, stability and yield of expression. {C}andidate antigens from the pre-clinical development expressed in {H}igh-{F}ive insect cells using the baculovirus expression vector system were transitioned into the {D}rosophila {S}chneider-2 cell ({S}2) expression-system compliant with clinical development. {T}he functional capacity of antibodies against antigens expressed in {H}igh-{F}ive cells or in {S}2 cells was equivalent. {T}his enabled an extensive down-selection of {S}2 insect cell-expressed antigens primarily encompassing the minimal {CSA}-binding region of {VAR}2{CSA}. {I}n general, we found differential potency of inhibitory antibodies against antigens with the same borders but of different var2csa sequences. {L}ikewise, we found that subtle size differences in antigens of the same sequence gave varying levels of inhibitory antibodies. {T}he study shows that induction of a functional response against recombinant subunits of the {VAR}2{CSA} antigen is unpredictable, demonstrating the need for large-scale screening in order to identify antigens that induce a broadly strain-transcending antibody response.},
  keywords = {},
  booktitle = {},
  journal = {{P}los {O}ne},
  volume = {10},
  numero = {9},
  pages = {e0135406 [12 p.]},
  ISSN = {1932-6203},
  year = {2015},
  DOI = {10.1371/journal.pone.0135406},
  URL = {https://www.documentation.ird.fr/hor/fdi:010065258},
}