{"doi":"10.1021/acschembio.5c00253","title":"Design of Hyperglycosylated Zika Virus E Proteins that Focus Antibody Recognition on the Complex E Dimer Epitope","abstract":"mosquitoes. ZIKV infection can cause Guillain-Barré syndrome and microcephaly, while severe dengue can lead to hemorrhagic fever and death. DENV infection of ZIKV-immune individuals is linked to severe clinical outcomes due to antibody-dependent enhancement (ADE) of infection. Thus, the development of broadly protective vaccines is an important objective. We focus on the E dimer epitope (EDE) of ZIKV, which is targeted by broadly neutralizing antibodies that protect against ZIKV and DENV1-4. We engineered ZIKV E dimer variants containing non-native asparagine-linked glycosylation sites to block antibody responses to regions outside the EDE using a structure-based iterative design approach. One candidate, SC30m53, bound EDE mAbs but not other mAbs and induced a potently neutralizing response against ZIKV and moderately cross-neutralizing responses against DENV1-3 in mice. These findings suggest that hyperglycosylation provides a promising approach to focusing the immune response on key epitopes.","journal":"ACS Chemical Biology","year":2025,"id":532826,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"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":878756,"name":"Matthew G. Hvasta","orcid":"0000-0001-7363-4344","position":1,"is_corresponding":false},{"id":437338,"name":"Kimberly A. Dowd","orcid":"0000-0003-3641-6852","position":2,"is_corresponding":false},{"id":181009,"name":"W. HUANG","orcid":null,"position":3,"is_corresponding":false},{"id":878241,"name":"Helen S. Jung","orcid":"0000-0003-0863-6460","position":4,"is_corresponding":false},{"id":1414337,"name":"Lamount R. Evanson","orcid":"0009-0008-8250-7011","position":5,"is_corresponding":false},{"id":240443,"name":"George I. Georgiev","orcid":"0000-0002-1323-7600","position":6,"is_corresponding":false},{"id":518064,"name":"Julia C. Frei","orcid":"0000-0002-4239-1586","position":7,"is_corresponding":false},{"id":217892,"name":"Jonathan F. Lovell","orcid":"0000-0002-9052-884X","position":8,"is_corresponding":false},{"id":106870,"name":"Theodore C. Pierson","orcid":"0000-0002-3795-4348","position":9,"is_corresponding":false},{"id":114738,"name":"Brian Kuhlman","orcid":"0000-0003-4907-9699","position":10,"is_corresponding":false},{"id":240446,"name":"Jonathan R. Lai","orcid":"0000-0002-4863-0015","position":11,"is_corresponding":false},{"id":28923,"name":"Margarette C. Mariano","orcid":"0000-0002-8331-0156","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:51:27.893975Z","pmid":"40848299","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":[]}