Title |
Characterization of a novel inhibitory human monoclonal antibody directed against Plasmodium falciparum Apical Membrane Antigen 1
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Published in |
Scientific Reports, December 2016
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DOI | 10.1038/srep39462 |
Pubmed ID | |
Authors |
Dominika J. Maskus, Michał Królik, Susanne Bethke, Holger Spiegel, Stephanie Kapelski, Melanie Seidel, Otchere Addai-Mensah, Andreas Reimann, Torsten Klockenbring, Stefan Barth, Rainer Fischer, Rolf Fendel |
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 IC50-value of 35 μg/ml (95% confidence interval: 33 μg/ml-37 μg/ml), which is three to eight times lower than the IC50-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. |
X Demographics
Geographical breakdown
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United States | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
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Unknown | 57 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 13 | 23% |
Student > Bachelor | 10 | 18% |
Researcher | 8 | 14% |
Student > Master | 7 | 12% |
Professor | 5 | 9% |
Other | 7 | 12% |
Unknown | 7 | 12% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 17 | 30% |
Immunology and Microbiology | 12 | 21% |
Biochemistry, Genetics and Molecular Biology | 9 | 16% |
Medicine and Dentistry | 3 | 5% |
Engineering | 2 | 4% |
Other | 5 | 9% |
Unknown | 9 | 16% |