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Foot-and-mouth disease virus antigenic landscape and reduced immunogenicity elucidated in atomic detail

Author

Listed:
  • Haozhou Li

    (Chinese Academy of Agricultural Sciences)

  • Pan Liu

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

  • Hu Dong

    (Chinese Academy of Agricultural Sciences)

  • Aldo Dekker

    (Wageningen University & Research)

  • Michiel M. Harmsen

    (Wageningen University & Research)

  • Huichen Guo

    (Chinese Academy of Agricultural Sciences)

  • Xiangxi Wang

    (Chinese Academy of Sciences)

  • Shiqi Sun

    (Chinese Academy of Agricultural Sciences)

Abstract

Unlike most other picornaviruses, foot-and-mouth disease (FMD) intact virions (146S) dissociate easily into small pentameric subunits (12S). This causes a dramatically decreased immunogenicity by a mechanism that remains elusive. Here, we present the high-resolution structures of 12S (3.2 Å) and its immune complex of a single-domain antibody (VHH) targeting the particle interior (3.2 Å), as well as two 146S-specific VHHs complexed to distinct sites on the 146S capsid surface (3.6 Å and 2.9 Å). The antigenic landscape of 146S is depicted using 13 known FMD virus-antibody complexes. Comparison of the immunogenicity of 146S and 12S in pigs, focusing on the resulting antigenic sites and incorporating structural analysis, reveals that dissociation of 146S leads to structural alteration and destruction of multiple epitopes, resulting in significant differences in antibody profiles/lineages induced by 12S and 146S. Furthermore, 146S generates higher synergistic neutralizing antibody titers compared to 12S, whereas both particles induce similar total FMD virus specific antibody titers. This study can guide the structure-based rational design of novel multivalent and broad-spectrum recombinant vaccines for protection against FMD.

Suggested Citation

  • Haozhou Li & Pan Liu & Hu Dong & Aldo Dekker & Michiel M. Harmsen & Huichen Guo & Xiangxi Wang & Shiqi Sun, 2024. "Foot-and-mouth disease virus antigenic landscape and reduced immunogenicity elucidated in atomic detail," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53027-5
    DOI: 10.1038/s41467-024-53027-5
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    1. Abhay Kotecha & Quan Wang & Xianchi Dong & Serban L. Ilca & Marina Ondiviela & Rao Zihe & Julian Seago & Bryan Charleston & Elizabeth E. Fry & Nicola G. A. Abrescia & Timothy A. Springer & Juha T. Hui, 2017. "Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus," Nature Communications, Nature, vol. 8(1), pages 1-8, August.
    2. Longfa Xu & Qingbing Zheng & Shaowei Li & Maozhou He & Yangtao Wu & Yongchao Li & Rui Zhu & Hai Yu & Qiyang Hong & Jie Jiang & Zizhen Li & Shuxuan Li & Huan Zhao & Lisheng Yang & Wangheng Hou & Wei Wa, 2017. "Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    3. Kang Wang & Binyang Zheng & Li Zhang & Lunbiao Cui & Xuan Su & Qian Zhang & Zhenxi Guo & Yu Guo & Wei Zhang & Ling Zhu & Fengcai Zhu & Zihe Rao & Xiangxi Wang, 2020. "Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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