Increased macrophage phagocytic activity with TLR9 agonist conjugation of an anti- Borrelia burgdorferi monoclonal antibody
Copyright © 2022. Published by Elsevier Inc.
| Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 246(2023) vom: 01. Jan., Seite 109180 |
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| Auteur principal: | |
| Autres auteurs: | , , , , , , , , , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2023
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| Accès à la collection: | Clinical immunology (Orlando, Fla.) |
| Sujets: | Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't BmpA Borrelia burgdorferi Lyme Lyme disease Macrophage Phagocytosis TLR9 plus... |
| Résumé: | Copyright © 2022. Published by Elsevier Inc. Borrelia burgdorferi (Bb) infection causes Lyme disease, for which there is need for more effective therapies. Here, we sequenced the antibody repertoire of plasmablasts in Bb-infected humans. We expressed recombinant monoclonal antibodies (mAbs) representing the identified plasmablast clonal families, and identified their binding specificities. Our recombinant anti-Bb mAbs exhibit a range of activity in mediating macrophage phagocytosis of Bb. To determine if we could increase the macrophage phagocytosis-promoting activity of our anti-Bb mAbs, we generated a TLR9-agonist CpG-oligo-conjugated anti-BmpA mAb. We demonstrated that our CpG-conjugated anti-BmpA mAb exhibited increased peak Bb phagocytosis at 12-24 h, and sustained macrophage phagocytosis over 60+ hrs. Further, our CpG-conjugated anti-BmpA mAb induced macrophages to exhibit a sustained activation morphology. Our findings demonstrate the potential for TLR9-agonist CpG-oligo conjugates to enhance mAb-mediated clearance of Bb, and this approach might also enhance the activity of other anti-microbial mAbs |
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| Description: | Date Completed 17.01.2023 Date Revised 12.02.2023 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2022.109180 |