Central Laboratory, Shanxi Province Hospital of Traditional Chinese Medicine, Taiyuan, China.
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
PLoS One. 2024 Oct 25;19(10):e0311137. doi: 10.1371/journal.pone.0311137. eCollection 2024.
Cervical cancer ranks as the third most prevalent malignancy in women worldwide. The persistence of Human papillomavirus (HPV) infection stands out as the foremost risk factor for cervical cancer development. Among the numerous HPV subtypes, HPV16 infection emerges as the primary pathogenic determinant of cervical cancer. To date, no specific drugs have been approved. In this study, we engineered two high-affinity fusion protein targeting HPV16 L1 protein based on the alpaca-derived single-domain antibody 2C12 previously obtained in our laboratory. These two fusion proteins exhibited potent neutralizing activity against HPV16 pseudovirus with IC50 values of 7.8 nM and 6.5 nM, respectively. Molecular docking analysis revealed that 2C12 formed ten pairs of hydrogen bonds with HPV16 L1, among which Arg39 and Thr100 established multiple pairs of hydrogen bonds with HPV16 L1, indicating their crucial roles in antigen-antibody binding process. These structural and biological findings underscore the effective binding capacity of these fusion proteins to HPV16, leading to reduced viral load and providing valuable insights into therapeutic antibody and vaccine development against HPV 16 infection.
宫颈癌是全球女性第三大常见恶性肿瘤。人乳头瘤病毒（HPV）感染持续存在是宫颈癌发展的首要危险因素。在众多 HPV 亚型中，HPV16 感染是宫颈癌的主要致病决定因素。迄今为止，尚无特定药物获得批准。在这项研究中，我们基于实验室先前获得的羊驼来源的单域抗体 2C12 ，设计了两种针对 HPV16 L1 蛋白的高亲和力融合蛋白。这两种融合蛋白对 HPV16 假病毒具有强大的中和活性，IC50 值分别为 7.8 nM 和 6.5 nM。分子对接分析表明，2C12 与 HPV16 L1 形成了十对氢键，其中 Arg39 和 Thr100 与 HPV16 L1 建立了多对氢键，表明它们在抗原-抗体结合过程中起着关键作用。这些结构和生物学发现强调了这些融合蛋白与 HPV16 的有效结合能力，从而降低了病毒载量，并为针对 HPV16 感染的治疗性抗体和疫苗开发提供了有价值的见解。
