Antibodies from dengue patients with prior exposure to Japanese encephalitis virus are broadly neutralizing against Zika virus

Gielenny M. Salem, Jedhan Ucat Galula, Shang Rung Wu, Jyung Hurng Liu, Yen Hsu Chen, Wen Hung Wang, Sheng Fan Wang, Cheng Sheng Song, Fan Chi Chen, Adrian B. Abarientos, Guan Wen Chen, Cheng Yi Wang, Day Yu Chao

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Exposure to multiple mosquito-borne flaviviruses within a lifetime is not uncommon; however, how sequential exposures to different flaviviruses shape the cross-reactive humoral response against an antigen from a different serocomplex has yet to be explored. Here, we report that dengue-infected individuals initially primed with the Japanese encephalitis virus (JEV) showed broad, highly neutralizing potencies against Zika virus (ZIKV). We also identified a rare class of ZIKV-cross-reactive human monoclonal antibodies with increased somatic hypermutation and broad neutralization against multiple flaviviruses. One huMAb, K8b, binds quaternary epitopes with heavy and light chains separately interacting with overlapping envelope protein dimer units spanning domains I, II, and III through cryo-electron microscopy and structure-based mutagenesis. JEV virus-like particle immunization in mice further confirmed that such cross-reactive antibodies, mainly IgG3 isotype, can be induced and proliferate through heterologous dengue virus (DENV) serotype 2 virus-like particle stimulation. Our findings highlight the role of prior immunity in JEV and DENV in shaping the breadth of humoral response and provide insights for future vaccination strategies in flavivirus-endemic countries.

原文English
文章編號15
期刊Communications Biology
7
發行號1
DOIs
出版狀態Published - 2024 12月

All Science Journal Classification (ASJC) codes

  • 醫藥(雜項)
  • 一般生物化學,遺傳學和分子生物學
  • 一般農業與生物科學

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