{"doi":"10.1016/j.celrep.2025.116098","title":"Identification of the seven critical residues that control ZIKV-DENV cross-reactivity to engineer a non-cross-reactive ZIKV vaccine","abstract":"The development of a Zika virus (ZIKV) vaccine is complicated by the high homology between ZIKV and dengue virus (DENV) envelope (E) proteins, resulting in immunological cross-reactivity that can exacerbate disease through antibody-dependent enhancement (ADE). Here, we screen 121 anti-DENV monoclonal antibodies (mAbs) for cross-reactivity with ZIKV E proteins. We identify 70 cross-reactive mAbs, 66 of which have epitopes that included at least one of seven E protein residues conserved among DENV1-DENV4 and ZIKV (R73, E79, W101, L107, F108, K110, and W212), establishing these residues as the key determinants of DENV-ZIKV cross-reactivity. Using these data, we engineer a ZIKV E protein variant with 10 mutations (\"ZIKVm10\") that reduces cross-reactivity with DENV mAbs in vitro and minimizes the induction of anti-DENV antibodies in immunized mice. Passive serum transfer from ZIKVm10-immunized mice confers near-complete protection against lethal ZIKV challenge and reduced ADE for DENV infection, providing a pathway for improved ZIKV vaccine design.","journal":"Cell Reports","year":2025,"id":528583,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9627,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":792762,"name":"Srikar Reddy","orcid":null,"position":1,"is_corresponding":false},{"id":352064,"name":"Agnès L. Chénine","orcid":null,"position":2,"is_corresponding":false},{"id":442719,"name":"J. Charles Whitbeck","orcid":null,"position":3,"is_corresponding":false},{"id":885371,"name":"Sonya Jacobsen","orcid":null,"position":4,"is_corresponding":false},{"id":1406918,"name":"Allison Sheetz","orcid":null,"position":5,"is_corresponding":false},{"id":625393,"name":"Kyle Doolan","orcid":"0000-0001-8449-4826","position":6,"is_corresponding":false},{"id":1227683,"name":"Diana M. Norden","orcid":null,"position":7,"is_corresponding":false},{"id":402846,"name":"Nolan Frey","orcid":"0000-0002-1889-1724","position":8,"is_corresponding":false},{"id":441734,"name":"Frederick W. Holtsberg","orcid":"0000-0001-5530-9943","position":9,"is_corresponding":false},{"id":441735,"name":"M. Javad Aman","orcid":"0000-0001-6977-4707","position":10,"is_corresponding":false},{"id":217936,"name":"Katja Fink","orcid":"0000-0002-3571-0390","position":11,"is_corresponding":false},{"id":106529,"name":"Michael Diamond","orcid":"0000-0002-8791-3165","position":12,"is_corresponding":false},{"id":62205,"name":"John S. Schieffelin","orcid":"0000-0001-6642-5739","position":13,"is_corresponding":false},{"id":106531,"name":"James E. Crowe","orcid":"0000-0002-0049-1079","position":14,"is_corresponding":false},{"id":283937,"name":"Edgar Davidson","orcid":"0000-0002-3333-2314","position":15,"is_corresponding":false},{"id":283938,"name":"Benjamin J. Doranz","orcid":"0000-0002-8245-3083","position":16,"is_corresponding":false},{"id":1406917,"name":"Ariadna Grinyo-Escuer","orcid":null,"position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:50:48.492873Z","pmid":"40753572","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}