Phage display-derived alpaca nanobodies as potential therapeutics for Naja atra snake envenomation

Wei Chu Wang, Jungshan Chang, Chi Hsin Lee, Yu Wei Chiang, Sy Jye Leu, Yan Chiao Mao, Jen Ron Chiang, Chun Kai Yang, Chao Jung Wu, Yi Yuan Yang

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.
原文英語
期刊Applied and Environmental Microbiology
90
發行號8
DOIs
出版狀態已發佈 - 8月 1 2024

ASJC Scopus subject areas

  • 生物技術
  • 食品科學
  • 應用微生物與生物技術
  • 生態學

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