{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T09:55:23Z","timestamp":1781776523685,"version":"3.54.5"},"posted":{"date-parts":[[2026,6,1]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH NIAID","award":["R01AI86073"],"award-info":[{"award-number":["R01AI86073"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Antibody-dependent enhancement (ADE) is a major concern across orthoflavivirus infections, yet how multiple viral exposures shape enhancement risk remains incompletely understood. Here, we integrated serosurveillance from Sa\u00fade, Brazil with functional immunologic analyses to define how yellow fever virus (YFV)-associated orthoflavivirus immune histories influence ADE phenotypes. Using serocomplex-specific anti-premembrane antibody profiling validated by microneutralization assays, plasma samples were stratified into YFV-only, YFV+DENV, and YFV+DENV+ZIKV exposure groups. In Fc\u03b3 receptor-bearing U937 cells, YFV-only plasma demonstrated minimal enhancement activity, whereas cumulative orthoflavivirus exposure generated broader ADE phenotypes across heterologous viruses. In\n                  <jats:italic>\n                    IFNAR1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  passive-transfer models, YFV-only plasma did not enhance ZIKV or DENV2 infection in vivo. In contrast, YFV+DENV plasma increased ZIKV viremia and accelerated mortality kinetics, while YFV+DENV+ZIKV plasma demonstrated concentration-dependent enhancement phenotypes. Collectively, these findings indicate that isolated YFV immunity does not predispose to ADE, whereas cumulative orthoflavivirus exposure generates antibody repertoires capable of producing concentration-dependent enhancement in vivo.\n                <\/jats:p>","DOI":"10.64898\/2026.05.22.26353817","type":"posted-content","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:10:12Z","timestamp":1780330212000},"source":"Crossref","is-referenced-by-count":0,"title":["Multiple, but not isolated, yellow fever virus-associated orthoflavivirus immune histories drive antibody-dependent enhancement of Zika and dengue viruses"],"prefix":"10.64898","author":[{"given":"Sebastian","family":"Gallon","sequence":"first","affiliation":[{"name":"Rutgers Global Health Institute, Rutgers University, New Brunswick, NJ, USA"},{"name":"Department of Medicine, Division of Allergy, Immunology, and Infectious Diseases and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prince Baffour","family":"Tonto","sequence":"additional","affiliation":[{"name":"Rutgers Global Health Institute, Rutgers University, New Brunswick, NJ, USA"},{"name":"Department of Medicine, Division of Allergy, Immunology, and Infectious Diseases and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifeng","family":"Ding","sequence":"additional","affiliation":[{"name":"Rutgers Global Health Institute, Rutgers University, New Brunswick, NJ, USA"},{"name":"Department of Medicine, Division of Allergy, Immunology, and Infectious Diseases and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailee","family":"Naito-Keoho","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Brites","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Infectologia (LAPI)-School of Medicine, Universidade Federal da Bahia, Salvador, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Martins","family":"Netto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Infectologia (LAPI)-School of Medicine, Universidade Federal da Bahia, Salvador, Bahia, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Kung","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. 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