Carias L.L., Dechavanne S., Nicolete C.V., Sreng S., Suon S., Amaratunga C., Fairhurst R.M., Dechavanne Célia, Barnes S., Witkowski B., Popovici J., Roesch C., Chen E., Ferreira M.U., Tolia N.H., Adams J.H., King C.L. (2019). Identification and characterization of functional human monoclonal antibodies to Plasmodium vivax Duffy-binding protein. Journal of Immunology, 202 (9), p. 2648-2660. ISSN 0022-1767.
Titre du document
Identification and characterization of functional human monoclonal antibodies to Plasmodium vivax Duffy-binding protein
Année de publication
2019
Auteurs
Carias L.L., Dechavanne S., Nicolete C.V., Sreng S., Suon S., Amaratunga C., Fairhurst R.M., Dechavanne Célia, Barnes S., Witkowski B., Popovici J., Roesch C., Chen E., Ferreira M.U., Tolia N.H., Adams J.H., King C.L.
Source
Journal of Immunology, 2019,
202 (9), p. 2648-2660 ISSN 0022-1767
Plasmodium vivax invasion of reticulocytes relies on distinct receptor-ligand interactions between the parasite and host erythrocytes. Engagement of the highly polymorphic domain II of the P. vivax Duffy-binding protein (DBPII) with the erythrocyte's Duffy Ag receptor for chemokines (DARC) is essential. Some P vivax-exposed individuals acquired Abs to DBPII that block DBPIIDARC interaction and inhibit P vivax reticulocyte invasion, and Ab levels correlate with protection against P. vivax malaria. To better understand the functional characteristics and fine specificity of protective human Abs to DBPII, we sorted single DBPII-specific IgG(+) memory B cells from three individuals with high blocking activity to DBPII. We identified 12 DBPII-specific human mAbs from distinct lineages that blocked DBPII-DARC binding. All mAbs were P. vivax strain transcending and targeted known binding motifs of DBPII with DARC. Eleven mAbs competed with each other for binding, indicating recognition of the same or overlapping epitopes. Naturally acquired blocking Abs to DBPII from individuals with high levels residing in different P vivax- endemic areas worldwide competed with mAbs, suggesting broadly shared recognition sites. We also found that mAbs inhibited P. vivax entry into reticulocytes in vitro. These findings suggest that IgG(+) memory B cell activity in individuals with P vivax strain- transcending Abs to DBPII display a limited clonal response with inhibitory blocking directed against a distinct region of the molecule.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010078697]
Identifiant IRD
fdi:010078697
