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

Clin Immunol. 2022 Nov 14:109180. doi: 10.1016/j.clim.2022.109180. Online ahead of print.ABSTRACTBorrelia 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.PMID:36396013 | DOI:10.1016/j.clim.2022.109180

Source: Clinical Immunology - November 17, 2022 Category: Allergy & Immunology Authors: Shaghayegh Jahanbani Paige S Hansen Lisa K Blum Effie E Bastounis Nitya S Ramadoss Mallesh Pandrala Jessica Marie Kirschmann Grace Sisemore Blacker Zelda Z Love Irving L Weissman Fahimeh Nemati Michal Caspi Tal William H Robinson Source Type: research