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Characterization of a novel inhibitory human monoclonal antibody directed against Plasmodium falciparum Apical Membrane Antigen 1.
- Source :
-
Scientific reports [Sci Rep] 2016 Dec 21; Vol. 6, pp. 39462. Date of Electronic Publication: 2016 Dec 21. - Publication Year :
- 2016
-
Abstract
- Malaria remains a major challenge to global health causing extensive morbidity and mortality. Yet, there is no efficient vaccine and the immune response remains incompletely understood. Apical Membrane Antigen 1 (AMA1), a leading vaccine candidate, plays a key role during merozoite invasion into erythrocytes by interacting with Rhoptry Neck Protein 2 (RON2). We generated a human anti-AMA1-antibody (humAbAMA1) by EBV-transformation of sorted B-lymphocytes from a Ghanaian donor and subsequent rescue of antibody variable regions. The antibody was expressed in Nicotiana benthamiana and in HEK239-6E, characterized for binding specificity and epitope, and analyzed for its inhibitory effect on Plasmodium falciparum. The generated humAbAMA1 shows an affinity of 106-135 pM. It inhibits the parasite strain 3D7A growth in vitro with an expression system-independent IC <subscript>50</subscript> -value of 35 μg/ml (95% confidence interval: 33 μg/ml-37 μg/ml), which is three to eight times lower than the IC <subscript>50</subscript> -values of inhibitory antibodies 4G2 and 1F9. The epitope was mapped to the close proximity of the RON2-peptide binding groove. Competition for binding between the RON2-peptide and humAbAMA1 was confirmed by surface plasmon resonance spectroscopy measurements. The particularly advantageous inhibitory activity of this fully human antibody might provide a basis for future therapeutic applications.
- Subjects :
- B-Lymphocytes parasitology
Binding, Competitive
Cell Line
Epitopes immunology
Erythrocytes immunology
Humans
Immunoglobulin G immunology
Inhibitory Concentration 50
Leukocytes, Mononuclear parasitology
Molecular Conformation
Protein Binding
Surface Plasmon Resonance
Nicotiana
Antibodies, Monoclonal immunology
Antigens, Protozoan immunology
Erythrocytes parasitology
Membrane Proteins immunology
Plasmodium falciparum immunology
Protozoan Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28000709
- Full Text :
- https://doi.org/10.1038/srep39462