Vaccine and Emerging Infections Research, Human Health Therapeutics Research Centre, National Research Council, Ottawa, Ontario K1A 0R6, Canada.
Division of Bioanalytical Chemistry, Priority Research Area Infections, Research Center Borstel, Leibniz Lung Center, 23845 Borstel, Germany.
ACS Chem Biol. 2020 Apr 17;15(4):1050-1058. doi: 10.1021/acschembio.0c00066. Epub 2020 Apr 1.
is an anaerobic Gram-positive, spore-forming nosocomial, gastrointestinal pathogen causing -associated disease with symptoms ranging from mild cases of antibiotic-associated diarrhea to fatal pseudomembranous colitis. We developed murine monoclonal antibodies (mAbs) specific for a conserved cell surface antigen, lipoteichoic acid (LTA)of . The mAbs were characterized in terms of their thermal stability, solubility, and their binding to LTA by surface plasmon resonance and competitive ELISA. Synthetic LTA molecules were prepared in order to better define the minimum epitope required to mimic the natural antigen, and three repeat units of the polymer were required for optimal recognition. One of the murine mAbs was chimerized with human constant region domains and was found to recognize the target antigen identically to the mouse version. These mAbs may be useful as therapeutics (standalone, in conjunction with known antitoxin approaches, or as delivery vehicles for antibody drug conjugates targeting the bacterium), as diagnostic agents, and in infection control applications.
艰难梭菌是一种厌氧的革兰氏阳性、产芽孢的医院获得性胃肠道病原体，可引起与艰难梭菌相关的疾病，症状范围从轻度抗生素相关性腹泻到致命的伪膜性结肠炎。我们开发了针对艰难梭菌保守细胞表面抗原脂磷壁酸（LTA）的鼠单克隆抗体（mAb）。mAb 的特征在于其热稳定性、溶解度以及通过表面等离子体共振和竞争性 ELISA 与 LTA 的结合。为了更好地定义模拟天然抗原所需的最小表位，制备了合成 LTA 分子，并且需要该聚合物的三个重复单元以实现最佳识别。其中一种鼠 mAb 与人恒定区结构域嵌合，并发现与鼠版本一样识别靶抗原。这些 mAb 可作为治疗剂（单独使用、与已知抗毒素方法联合使用或作为针对细菌的抗体药物偶联物的递送载体）、诊断剂和感染控制应用。
