Jeong Jieun, Kim Jae-Seok, Lee Junghyeon, Seo Yu Ri, Yi Eugene C, Kim Kristine M
Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon, Gangwon 24341, Korea.
Department of Laboratory Medicine, Kangdong Sacred Heart Hospital, Gangdong-gu, Seoul 05355, Korea.
Biomolecules. 2021 Mar 23;11(3):484. doi: 10.3390/biom11030484.
Gonorrhea is one of the most common, but still hidden and insidious, sexually transmitted diseases caused by (). However, the diagnosis and treatment of gonorrhea are hampered by antigenic variability among , the lack of acquired immunity, and antimicrobial resistance. Further, strains resistant to cephalosporins, including ceftriaxone, the last line of defense, represent a growing threat, which prompted us to develop -specific diagnostic antibodies with broad-spectrum binding to strains to generate gonorrhea-detecting reagents. This study reports the identification of antibodies via bio-panning on cells using scFv-phage libraries. Reformatting the lead scFv-phage Clones 1 and 4 to a multivalent scFv1-Fc-scFv4 maxibody increased the sensitivity by up to 20-fold compared to the single scFv-Fc (maxibody) alone. Moreover, the multivalent maxibody showed broader cross-reactivity with clinical isolates and the ceftriaxone antibiotic-resistant World Health Organization (WHO) reference strain L. In contrast, the selected antibodies in the scFv-phage, maxibody, and multivalent maxibody did not bind to , , and , suggesting the clinical and pharmaceutical diagnostic value of these selected antibodies for gonorrheal infections. The present study illustrates the advantages and potential application of multivalent maxibodies to develop rapid and sensitive diagnostic reagents for infectious diseases and cancer.
淋病是由（）引起的最常见但仍隐匿且潜伏的性传播疾病之一。然而，淋病的诊断和治疗受到（）之间抗原变异性、缺乏获得性免疫以及抗菌药物耐药性的阻碍。此外，对包括头孢曲松（最后一道防线）在内的头孢菌素耐药的菌株构成了日益严重的威胁，这促使我们开发与（）菌株具有广谱结合能力的特异性诊断抗体，以生产淋病检测试剂。本研究报告了通过使用单链抗体噬菌体文库在（）细胞上进行生物淘选来鉴定（）抗体的过程。将先导单链抗体噬菌体克隆1和4重新构建为多价单链抗体1- 免疫球蛋白Fc段 - 单链抗体4最大抗体，与单独的单链抗体 - 免疫球蛋白Fc段（最大抗体）相比，灵敏度提高了20倍。此外，多价最大抗体与临床分离株以及头孢曲松耐药的世界卫生组织（WHO）参考菌株L表现出更广泛的交叉反应性。相比之下，在单链抗体噬菌体、最大抗体和多价最大抗体中选择的抗体不与（）、（）和（）结合，这表明这些选择的抗体对淋病感染具有临床和药物诊断价值。本研究阐述了多价最大抗体在开发针对传染病和癌症的快速灵敏诊断试剂方面的优势和潜在应用。
