Jahanbani Shaghayegh, 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
Division of Immunology and Rheumatology, Stanford School of Medicine, Stanford, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA; Department of Biotechnology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Stem cell and Regenerative Medicine, Stanford School of Medicine, Stanford, CA, USA.
Clin Immunol. 2023 Jan;246:109180. doi: 10.1016/j.clim.2022.109180. Epub 2022 Nov 14.
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.
伯氏疏螺旋体（Bb）感染会引发莱姆病，对此需要更有效的治疗方法。在此，我们对Bb感染人类体内浆母细胞的抗体库进行了测序。我们表达了代表已鉴定浆母细胞克隆家族的重组单克隆抗体（mAb），并确定了它们的结合特异性。我们的重组抗Bb mAb在介导巨噬细胞对Bb的吞噬作用方面表现出一系列活性。为了确定我们是否能够增强抗Bb mAb促进巨噬细胞吞噬的活性，我们制备了一种与TLR9激动剂CpG寡核苷酸偶联的抗BmpA mAb。我们证明，我们的CpG偶联抗BmpA mAb在12 - 24小时时Bb吞噬峰值增加，并且在60多个小时内维持巨噬细胞的吞噬作用。此外，我们的CpG偶联抗BmpA mAb诱导巨噬细胞呈现持续激活的形态。我们的研究结果表明，TLR9激动剂CpG寡核苷酸偶联物有增强mAb介导的Bb清除的潜力，并且这种方法也可能增强其他抗微生物mAb的活性。
