Cited by 14Mosquito-borne diseases and controlViral Infections and VectorsSARS-CoV-2 and COVID-19 Research

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

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Abstract

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.

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Metadata

Authors
Salem, G. M., Galula, J. U., Wu, S.-R., Liu, J.-H., Chen, Y.-H., Wang, W.-H., Wang, S.-F., Song, C.-S., Chen, F.-C., Abarientos, A. B., Chen, G.-W., Wang, C.-I., & Chao, D.-Y.
Affiliations
  • National Chung Hsing University (TW)
  • National Cheng Kung University (TW)
  • National Sun Yat-sen University (TW)
  • Kaohsiung Medical University (TW)
  • Agency for Science, Technology and Research (SG)
Corresponding author
Chao, Day-Yu
Venue
Communications Biology
Published
2024-01-24
Volume
7
Issue
1
Pages
15-15
ISSN
2399-3642 (ISSN-L)
OpenAlex
W4391168722
Cited by
14
References
1
Citations by year
2026: 7 · 2025: 5 · 2024: 2
FWCI
5.77
Type
journal article
Language
en
Open access
Locations
  • Communications Biology (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Ministry of Science and Technology, Taiwan (MOST-110-2313-B-005-041)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
Zika virus, Japanese encephalitis virus, dengue virus, cross-reactive antibodies, monoclonal antibodies, humoral immunity, flavivirus cross-reactivity, somatic hypermutation, quaternary epitope, heterologous immunity
MeSH terms
Zika Virus Infection, Zika Virus, Animals, Antibodies, Monoclonal, Dengue, Encephalitis Virus, Japanese, Humans, Cryoelectron Microscopy, Mice

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