title: Parity-dependent recognition of DBL1X-3X suggests an important role of the VAR2CSA high-affinity CSA-binding region in the development of the humoral response against placental malaria.
abstract: Plasmodium falciparum multidomain protein VAR2CSA stands today as the leading vaccine candidate against pregnancy-associated malaria (PAM). Most of the studies aiming to decrypt how naturally acquired immunity develops have assessed the immune recognition of individual VAR2CSA Duffy-binding-like (DBL) domains, thus overlooking the presence of conformational epitopes resulting from the overall folding of the full-length protein. In order to characterize the development of humoral immunity toward VAR2CSA, we made use of a large cohort of 293 Senegalese pregnant women to assess the level of recognition by plasma IgG of the full-length VAR2CSA protein of the 3D7 parasite strain (3D7-VAR2CSA), the CSA-binding multidomains 3D7-DBL1X to -DBL3X (3D7-DBL1X-3X), and the CSA nonbinding multidomains 3D7-DBL4ε to -DBL6ε (3D7-DBL4ε-6ε), as well as individual 3D7-DBL domains. Our results revealed a parity-dependent recognition of the full-length 3D7-VAR2CSA and of the CSA-binding region, 3D7-DBL1X-3X. Indeed, multigravid women possess significantly higher levels of antibodies directed against these constructs than primigravidae. Our 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 VAR2CSA-based vaccines.
authors.affiliation: Inserm UMR_1134, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France Institut National de la Transfusion Sanguine, Paris, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dechavanne
authors.affiliation: Inserm UMR_1134, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France Institut National de la Transfusion Sanguine, Paris, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Anand
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Inserm UMR_1134, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France Institut National de la Transfusion Sanguine, Paris, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gangnard
authors.affiliation: Inserm UMR_1134, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France Institut National de la Transfusion Sanguine, Paris, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Sofia
authors.initials: S
authors.lastname: Nunes-Silva
authors.affiliation: Inserm UMR_1134, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France Institut National de la Transfusion Sanguine, Paris, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Célia
authors.initials: C
authors.lastname: Dechavanne
authors.affiliation: Laboratory of Excellence GR-Ex, Paris, France Institut de Recherche pour le Développement, UMR_216, Mère et Enfant Face aux Infections Tropicales, Paris, France PRES Sorbonne Paris Cité, Faculté de Pharmacie, Paris, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Fievet
authors.affiliation: Laboratory of Excellence GR-Ex, Paris, France Institut de Recherche pour le Développement, UMR_216, Mère et Enfant Face aux Infections Tropicales, Paris, France PRES Sorbonne Paris Cité, Faculté de Pharmacie, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Deloron
authors.affiliation: Inserm UMR_1134, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France Institut National de la Transfusion Sanguine, Paris, France Laboratory of Excellence GR-Ex, Paris, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chêne
authors.affiliation: Inserm UMR_1134, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMR_S1134, Paris, France Institut National de la Transfusion Sanguine, Paris, France Laboratory of Excellence GR-Ex, Paris, France Benoit.gamain@inserm.fr.
authors.forename: Benoît
authors.initials: B
authors.lastname: Gamain
mesh_terms: D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D056724:Immunity, Humoral; D018445:Infectious Disease Transmission, Vertical; D016778:Malaria, Falciparum / Q000276:immunology*; D008875:Middle Aged; D010298:Parity; D010963:Plasmodium falciparum / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012675:Senegal / Q000453:epidemiology; D014157:Transcription Factors / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; C095472:ERCC8 protein, human; D014157:Transcription Factors; C512601:VAR2CSA protein, Plasmodium falciparum; D045643:DNA Repair Enzymes
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