Increased macrophage phagocytic activity with TLR9 agonist conjugation of an anti- Borrelia burgdorferi monoclonal antibody

Increased macrophage phagocytic activity with TLR9 agonist conjugation of an anti- Borrelia burgdorferi monoclonal antibody

Copyright © 2022. Published by Elsevier Inc.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 246(2023) vom: 01. Jan., Seite 109180
1. Verfasser: Jahanbani, Shaghayegh (VerfasserIn)
Weitere Verfasser: Hansen, Paige S, Blum, Lisa K, Bastounis, Effie E, Ramadoss, Nitya S, Pandrala, Mallesh, Kirschmann, Jessica Marie, Blacker, Grace Sisemore, Love, Zelda Z, Weissman, Irving L, Nemati, Fahimeh, Tal, Michal Caspi, Robinson, William H
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't BmpA Borrelia burgdorferi Lyme Lyme disease Macrophage Phagocytosis TLR9 mehr... Toll-Like Receptor 9 Antibodies, Monoclonal TLR9 protein, human
Beschreibung
Zusammenfassung: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
Beschreibung: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