Human Vaccines & Immunotherapeutics (Dec 2024)

Characterization of neutralizing chimeric heavy-chain antibodies against tetanus toxin

  • Kexuan Cheng,
  • Jiansheng Lu,
  • Jiazheng Guo,
  • Rong Wang,
  • Lei Chen,
  • Xi Wang,
  • Yujia Jiang,
  • Yating Li,
  • Changyan Xu,
  • Qinglin Kang,
  • Gulisaina Qiaerxie,
  • Peng Du,
  • Chen Gao,
  • Yunzhou Yu,
  • Zhixin Yang,
  • Wei Wang

DOI
https://doi.org/10.1080/21645515.2024.2366641
Journal volume & issue
Vol. 20, no. 1

Abstract

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Tetanus toxin (TeNT) is one of the most toxic proteins. Neutralizing antibodies against TeNT are effective in prevention and treatment. In this study, 14 anti-tetanus nanobodies were obtained from a phage display nanobody library by immunizing a camel with the C-terminal receptor-binding domain of TeNT (TeNT-Hc) as the antigen. After fusion with the human Fc fragment, 11 chimeric heavy-chain antibodies demonstrated nanomolar binding toward TeNT-Hc. The results of toxin neutralization experiments showed that T83–7, T83–8, and T83–13 completely protected mice against 20 × the median lethal dose (LD50) at a low concentration. The neutralizing potency of T83–7, T83–8, and T83–13 against TeNT is 0.4 IU/mg, 0.4 IU/mg and 0.2 IU/mg, respectively. In the prophylactic setting, we found that 5 mg/kg of T83–13 provided the mice with full protection from tetanus, even when they were injected 14 days before exposure to 20 × LD50 TeNT. T83–7 and T83–8 were less effective, being fully protective only when challenged 7 or 10 days before exposure, respectively. In the therapeutic setting, 12 h after exposure to TeNT, 1 ~ 5 mg/kg of T83–7, and T83–8 could provide complete protection for mice against 5 × LD50 TeNT, while 1 mg/kg T83–13 could provide complete protection 24 h after exposure to 5 × LD50 TeNT. Our results suggested that these antibodies represent prophylactic and therapeutic activities against TeNT in a mouse model. The T83–7, T83–8, and T83–13 could form the basis for the subsequent development of drugs to treat TeNT toxicity.

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