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However, it remains unclear whether the antigenic distances between an individual\u2019s first infection and subsequent exposures dictate disease risk, explaining the observed large-scale differences in dengue hospitalizations across years. Here, we develop a framework that combines detailed antigenic and genetic characterization of viruses with details on hospitalized cases from 21 years of dengue surveillance in Bangkok, Thailand, to identify the role of the antigenic profile of circulating viruses in determining disease risk. We found that the risk of hospitalization depended on both the specific order of infecting serotypes and the antigenic distance between an individual\u2019s primary and secondary infections, with risk maximized at intermediate antigenic distances. These findings suggest that immune imprinting helps determine dengue disease risk and provide a pathway to monitor the changing risk profile of populations and to quantifying risk profiles of candidate vaccines.<\/jats:p>","DOI":"10.1126\/scitranslmed.adk3259","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T13:58:10Z","timestamp":1713967090000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":28,"title":["Antigenic distance between primary and secondary dengue infections correlates with disease risk"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5371-2138","authenticated-orcid":true,"given":"Lin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Genetics, University of Cambridge, Cambridge CB2 1TN, 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-0173","authenticated-orcid":true,"given":"Richard","family":"Jarman","sequence":"additional","affiliation":[{"name":"Coalition for Epidemic Preparedness Initiative, Washington, DC 20006, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2712-7960","authenticated-orcid":true,"given":"Matthew A.","family":"Conte","sequence":"additional","affiliation":[{"name":"Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8555-5352","authenticated-orcid":true,"given":"Irina Maljkovic","family":"Berry","sequence":"additional","affiliation":[{"name":"Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, 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Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0069-3738","authenticated-orcid":true,"given":"Piyarat","family":"Suntarattiwong","sequence":"additional","affiliation":[{"name":"Queen Sirikit National Institute of Child Health, Bangkok 10400, Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warunee","family":"Vandepitte","sequence":"additional","affiliation":[{"name":"Queen Sirikit National Institute of Child Health, Bangkok 10400, Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6707-482X","authenticated-orcid":true,"given":"Stephen S.","family":"Whitehead","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, 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