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Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains

Author

Listed:
  • Li Chen

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Mengmeng Sun

    (University of Science and Technology of China)

  • Huajun Zhang

    (Chinese Academy of Sciences)

  • Xinghai Zhang

    (Chinese Academy of Sciences)

  • Yanfeng Yao

    (Chinese Academy of Sciences)

  • Ming Li

    (University of Science and Technology of China)

  • Kangyin Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Pengfei Fan

    (Beijing Institute of Biotechnology)

  • Haiwei Zhang

    (Chinese Academy of Sciences)

  • Ye Qin

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhe Zhang

    (Chinese Academy of Sciences)

  • Entao Li

    (University of Science and Technology of China
    University of Science and Technology of China
    Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases)

  • Zhen Chen

    (Chinese Academy of Sciences)

  • Wuxiang Guan

    (Chinese Academy of Sciences)

  • Shanshan Li

    (University of Science and Technology of China)

  • Changming Yu

    (Beijing Institute of Biotechnology)

  • Kaiming Zhang

    (University of Science and Technology of China
    Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases
    University of Science and Technology of China
    University of Science and Technology of China)

  • Rui Gong

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Hubei Jiangxia Laboratory)

  • Sandra Chiu

    (University of Science and Technology of China
    University of Science and Technology of China
    Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases)

Abstract

Nipah virus (NiV) is a World Health Organization priority pathogen and there are currently no approved drugs for clinical immunotherapy. Through the use of a naïve human phage-displayed Fab library, two neutralizing antibodies (NiV41 and NiV42) targeting the NiV receptor binding protein (RBP) were identified. Following affinity maturation, antibodies derived from NiV41 display cross-reactivity against both NiV and Hendra virus (HeV), whereas the antibody based on NiV42 is only specific to NiV. Results of immunogenetic analysis reveal a correlation between the maturation of antibodies and their antiviral activity. In vivo testing of NiV41 and its mature form (41-6) show protective efficacy against a lethal NiV challenge in hamsters. Furthermore, a 2.88 Å Cryo-EM structure of the tetrameric RBP and antibody complex demonstrates that 41-6 blocks the receptor binding interface. These findings can be beneficial for the development of antiviral drugs and the design of vaccines with broad spectrum against henipaviruses.

Suggested Citation

  • Li Chen & Mengmeng Sun & Huajun Zhang & Xinghai Zhang & Yanfeng Yao & Ming Li & Kangyin Li & Pengfei Fan & Haiwei Zhang & Ye Qin & Zhe Zhang & Entao Li & Zhen Chen & Wuxiang Guan & Shanshan Li & Chang, 2024. "Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47213-8
    DOI: 10.1038/s41467-024-47213-8
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    References listed on IDEAS

    as
    1. Oscar A. Negrete & Ernest L. Levroney & Hector C. Aguilar & Andrea Bertolotti-Ciarlet & Ronen Nazarian & Sara Tajyar & Benhur Lee, 2005. "EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus," Nature, Nature, vol. 436(7049), pages 401-405, July.
    2. Nicole A. Doria-Rose & Chaim A. Schramm & Jason Gorman & Penny L. Moore & Jinal N. Bhiman & Brandon J. DeKosky & Michael J. Ernandes & Ivelin S. Georgiev & Helen J. Kim & Marie Pancera & Ryan P. Staup, 2014. "Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies," Nature, Nature, vol. 509(7498), pages 55-62, May.
    3. Hua-Xin Liao & Rebecca Lynch & Tongqing Zhou & Feng Gao & S. Munir Alam & Scott D. Boyd & Andrew Z. Fire & Krishna M. Roskin & Chaim A. Schramm & Zhenhai Zhang & Jiang Zhu & Lawrence Shapiro & James C, 2013. "Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus," Nature, Nature, vol. 496(7446), pages 469-476, April.
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