{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:36:44Z","timestamp":1791398204360,"version":"4.3.3"},"reference-count":23,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"817","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,9,24]]},"abstract":"<jats:p>Dengue viruses (DENVs) cause 390 million infections annually, although only ~25% of these infections are symptomatic. Whereas antibody features linked to severe DENV disease are well studied, factors influencing infection susceptibility remain less clear. Here, we examined immunoglobulin G (IgG) characteristics before and after DENV vaccination (Dengvaxia) in individuals with a history of prior DENV exposure, comparing those who developed postvaccination infections to those who remained infection free. Elevated anti-DENV afucosylation, present before or after vaccination, was associated with increased likelihood of infection after vaccination. These data were further supported by mechanistic studies, which revealed that nonneutralizing, afucosylated, post-Dengvaxia IgG enhanced DENV replication in mice. This enhancement was dependent on CD16, the receptor for the afucosylated IgG Fc domain. Together, these findings support a model in which the presence of afucosylated IgG promotes virus replication, increasing the likelihood of productive infection upon DENV exposure. Moreover, these results highlight that IgG1 fucosylation is a predictor of risk for breakthrough DENV infection despite vaccination and support the importance of investigating strategies to regulate Fc fucosylation during vaccination.<\/jats:p>","DOI":"10.1126\/scitranslmed.adx7231","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T17:58:12Z","timestamp":1758736692000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Afucosylation of anti-dengue IgG is associated with enhanced susceptibility to dengue virus infection postvaccination"],"prefix":"10.1126","volume":"17","author":[{"given":"Usama","family":"Ashraf","sequence":"first","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-3757","authenticated-orcid":true,"given":"Saborni","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4371-8744","authenticated-orcid":true,"given":"Courtney","family":"Scallan","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5407-2005","authenticated-orcid":true,"given":"Nathan C.","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6493-190X","authenticated-orcid":true,"given":"Maria Theresa","family":"Alera","sequence":"additional","affiliation":[{"name":"Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2115-4493","authenticated-orcid":true,"given":"Aaron","family":"Farmer","sequence":"additional","affiliation":[{"name":"Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Noreen","family":"Cabalfin-Chua","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chong Hua Hospital, Cebu City, Cebu 6000, Philippines."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5882-5548","authenticated-orcid":true,"given":"Nelson L.","family":"Michael","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-6848","authenticated-orcid":true,"given":"Alan L.","family":"Rothman","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Institute for Immunology and Informatics, University of Rhode Island, Providence, RI 02903, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3894-685X","authenticated-orcid":true,"given":"Taia T.","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA."},{"name":"Department of Medicine, Division of Infectious Diseases, Stanford University School of Medicine, Stanford, CA 94305, USA."},{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12060"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006965"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-013-1645-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6836"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai8128"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc7303"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107642"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13109"},{"key":"e_1_3_2_10_2","doi-asserted-by":"crossref","unstructured":"R. Yamin K. S. Kao M. R. MacDonald T. Cantaert C. M. Rice J. V. Ravetch S. Bournazos Human Fc\u03b3RIIIa activation on splenic macrophages drives the in vivo pathogenesis of dengue disease. bioRxiv 514909 [Preprint] (2022). https:\/\/doi.org\/10.1101\/2022.11.02.514909.","DOI":"10.1101\/2022.11.02.514909"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.07.056"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix609"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61060-6"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01392-9"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2019.1658503"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01421-y"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1203954109"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2020.09.001"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2212658119"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abm7853"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.026"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr300887z"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00828-7"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003230"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adx7231","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T17:58:20Z","timestamp":1758736700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adx7231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":23,"journal-issue":{"issue":"817","published-print":{"date-parts":[[2025,9,24]]}},"alternative-id":["10.1126\/scitranslmed.adx7231"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adx7231","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]},"assertion":[{"value":"2025-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadx7231"}}