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

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Broadly neutralizing antibodies against Zika virus from dengue patients with prior exposure to Japanese encephalitis virus

Open access
Salem, Gielenny, Galula, Jedhan, Wu, Shang-Rung, Liu, Jyung, Chen, Yen-Hsu, Wang, Wen-Hung, Wang, Sheng-Fan, Song, Cheng-Sheng, Chen, Fan-Chi, Wang, Cheng-Yi, Chao, Day-Yu·2023·Communications Biology
DOI 10.21203/rs.3.rs-2969700/v1PMC PMC10808242

Preprint — published as 10.1038/s42003-023-05661-w · Paper page

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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 (CR) 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 broadly highly neutralizing potencies against the Zika virus (ZIKV). We also identified a rare class of ZIKV CR human monoclonal antibodies (huMAbs) 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 E dimer units spanning domains I, II, and III through cryo-electron microscopy and structure-based mutagenesis. Using JEV virus-like particle (VLP) immunization in mice further confirmed that such CR antibodies, mainly IgG3 isotype, can be induced and proliferate through heterologous DENV-2 VLP stimulation. Our findings provide novel insights for future vaccination strategies.

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Metadata

Authors
Salem, G., Galula, J., Wu, S.-R., Liu, J., Chen, Y.-H., Wang, W.-H., Wang, S.-F., Song, C.-S., Chen, F.-C., Wang, C.-Y., & 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
Corresponding author
Chao, Day-Yu
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2023-06-07
Volume
7
Issue
1
Pages
15-15
ISSN
2399-3642 (ISSN-L)
DOI
10.21203/rs.3.rs-2969700/v1
PMC
PMC10808242
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
Licence
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
  • Academia Sinica
  • Ministry of Science and Technology, Taiwan (MOST110-2313-B005-041)
  • National Cheng Kung University
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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