{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T13:28:30Z","timestamp":1787232510383,"version":"build-2736575974"},"reference-count":120,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572575"],"award-info":[{"award-number":["82572575"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82572575"],"award-info":[{"award-number":["82572575"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Yunnan Talent Support Plant","award":["202505AS350006"],"award-info":[{"award-number":["202505AS350006"]}]},{"DOI":"10.13039\/501100008871","name":"Yunnan Key Research and Development Program","doi-asserted-by":"publisher","award":["202501AS070022"],"award-info":[{"award-number":["202501AS070022"]}],"id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yunnan Provencial Key Laboratory of Cross-border Infectious Diseases Control & Drug Innovation","award":["2025KJ02"],"award-info":[{"award-number":["2025KJ02"]}]},{"name":"First-Class Discipline Team of Kunming Medical University","award":["2024XKTDYS09"],"award-info":[{"award-number":["2024XKTDYS09"]}]},{"award":["2024XKTDYS09"],"award-info":[{"award-number":["2024XKTDYS09"]}],"id":[{"id":"https:\/\/ror.org\/038c3w259","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Infections caused by flaviviruses, including dengue virus (DENV), Zika virus (ZIKV), and West Nile virus (WNV), can lead to severe hemorrhagic or neurological disease. Antibody-dependent enhancement (ADE) remains a major obstacle to the development of safe flavivirus vaccines and antibody-based therapeutics. ADE includes ADE of infection, in which antibodies increase in viral entry, replication, or infection load, and ADE of disease, in which antibody-dependent inflammatory and immunopathological responses exacerbate disease severity. Previous reviews have largely addressed the general virological and immunological mechanisms of ADE, but few have integrated antibody isotypes and subclasses, Fc-region modifications, Fc receptor diversity, host Fc\u03b3R polymorphisms, and complement activation within a translational framework. Consequently, how these factors jointly shape ADE of infection, progression to ADE of disease, and individual risk remains incompletely understood. Here, we synthesize evidence linking antibody properties, Fc receptor expression and signaling, Fc\u03b3R genetic variation, and complement regulation to both forms of ADE. We then discuss how these findings can inform antigen selection, Fc engineering, complement-informed intervention, and systems serology-based risk stratification. By connecting mechanistic evidence with vaccine and therapeutic development, this review offers a framework for designing safer flavivirus interventions and advancing individualized assessment of ADE risk.<\/jats:p>","DOI":"10.3390\/v18080916","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:57:53Z","timestamp":1787230673000},"page":"916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibody-Dependent Enhancement in Flavivirus Infections: From Fc Receptor Signaling to Vaccine and Therapeutic Design"],"prefix":"10.3390","volume":"18","author":[{"given":"Yiling","family":"Li","sequence":"first","affiliation":[{"name":"Yunnan Provincial Key Laboratory of Public Health and Biosafety, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"},{"name":"Yunnan Provencial Key Laboratory of Cross-Border Infectious Diseases Control & Drug Innovation, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zonghui","family":"Wu","sequence":"additional","affiliation":[{"name":"Yunnan Provincial Key Laboratory of Public Health and Biosafety, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"},{"name":"Yunnan Provencial Key Laboratory of Cross-Border Infectious Diseases Control & Drug Innovation, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchao","family":"Cha","sequence":"additional","affiliation":[{"name":"Yunnan Provincial Key Laboratory of Public Health and Biosafety, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"},{"name":"Yunnan Provencial Key Laboratory of Cross-Border Infectious Diseases Control & Drug Innovation, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3784-8067","authenticated-orcid":false,"given":"Wei","family":"Pang","sequence":"additional","affiliation":[{"name":"Yunnan Provincial Key Laboratory of Public Health and Biosafety, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"},{"name":"Yunnan Provencial Key Laboratory of Cross-Border Infectious Diseases Control & Drug Innovation, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5500-0329","authenticated-orcid":false,"given":"Le","family":"Sun","sequence":"additional","affiliation":[{"name":"Yunnan Provincial Key Laboratory of Public Health and Biosafety, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"},{"name":"Yunnan Provencial Key Laboratory of Cross-Border Infectious Diseases Control & Drug Innovation, Department of Pathogen Biology and Immunology, School of Basic Medicine, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1080\/21505594.2021.1996059","article-title":"Pathogenesis and virulence of flavivirus infections","volume":"12","author":"Heunis","year":"2021","journal-title":"Virulence"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1126\/science.4023707","article-title":"Nucleotide sequence of yellow fever virus: Implications for flavivirus gene expression and evolution","volume":"229","author":"Rice","year":"1985","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.antiviral.2009.10.008","article-title":"Present and future arboviral threats","volume":"85","author":"Weaver","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S398","DOI":"10.1093\/infdis\/jiad193","article-title":"A Prototype-Pathogen Approach for the Development of Flavivirus Countermeasures","volume":"228","author":"Kuhn","year":"2023","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bello, M.B., Alsaadi, A., Naeem, A., Almahboub, S.A., Bosaeed, M., and Aljedani, S.S. (2024). Development of nucleic acid-based vaccines against dengue and other mosquito-borne flaviviruses: The past, present, and future. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1475886"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3644","DOI":"10.1038\/s41467-018-06006-6","article-title":"Refined efficacy estimates of the Sanofi Pasteur dengue vaccine CYD-TDV using machine learning","volume":"9","author":"Dorigatti","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41577-024-01067-9","article-title":"Mechanisms of antibody-dependent enhancement of infectious disease","volume":"25","author":"Wells","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1038\/s41467-024-45806-x","article-title":"Prior flavivirus immunity skews the yellow fever vaccine response to cross-reactive antibodies with potential to enhance dengue virus infection","volume":"15","author":"Luppa","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sawant, J., Patil, A., and Kurle, S. (2023). A Review: Understanding Molecular Mechanisms of Antibody-Dependent Enhancement in Viral Infections. Vaccines, 11.","DOI":"10.3390\/vaccines11071240"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.1172\/JCI130029","article-title":"Functional diversification of IgGs through Fc glycosylation","volume":"129","author":"Wang","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wegman, A.D., Waldran, M.J., Bahr, L.E., Lu, J.Q., Baxter, K.E., Thomas, S.J., and Waickman, A.T. (2023). DENV-specific IgA contributes protective and non-pathologic function during antibody-dependent enhancement of DENV infection. PLoS Pathog., 19.","DOI":"10.1101\/2023.04.01.535210"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Pham, H.T., Pham, T.N.T., Tran, N.H.T., Ha, Q.D., Tran, D.K., Nguyen, N.H.D., Pham, V.H., and Pham, S.T. (2024). Dengue Hemorrhagic Fever in Quang Nam Province (Vietnam) from 2020 to 2022\u2014A Study on Serotypes Distribution and Immunology Factors. Diagnostics, 14.","DOI":"10.3390\/diagnostics14161772"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chelluboina, S., Kshirsagar, D., Panzade, G., Mishra, A.C., Arankalle, V., and Shrivastava, S. (2025). Evaluation of methods for the measurement of antibody-dependent enhancement of dengue virus infection using different Fc\u03b3RIIa expressing cell lines. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0331320"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Soto-Garita, C., Murillo, T., Hengel, H., and Corrales-Aguilar, E. (2025). Fc\u03b3RIIIA -activating antibodies in dengue virus infection reveals a distinct transient cross-reactive profile. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1662138"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3716","DOI":"10.1182\/blood-2008-09-179754","article-title":"Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses","volume":"113","author":"Bruhns","year":"2009","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/s41577-022-00813-1","article-title":"Beyond neutralization: Fc-dependent antibody effector functions in SARS-CoV-2 infection","volume":"23","author":"Zhang","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1128\/microbiolspec.MCHD-0045-2016","article-title":"The Role and Function of Fc\u03b3 Receptors on Myeloid Cells","volume":"4","author":"Bournazos","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"eabm3151","DOI":"10.1126\/scitranslmed.abm3151","article-title":"Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection","volume":"14","author":"Dias","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Malafa, S., Medits, I., Aberle, J.H., Aberle, S.W., Haslwanter, D., Tsouchnikas, G., W\u00f6lfel, S., Huber, K.L., Percivalle, E., and Cherpillod, P. (2020). Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008034"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10875-014-0022-7","article-title":"The long elusive IgM Fc receptor, Fc\u03bcR","volume":"34","author":"Kubagawa","year":"2014","journal-title":"J. Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wegman, A.D., Fang, H., Rothman, A.L., Thomas, S.J., Endy, T.P., McCracken, M.K., Currier, J.R., Friberg, H., Gromowski, G.D., and Waickman, A.T. (2021). Monomeric IgA Antagonizes IgG-Mediated Enhancement of DENV Infection. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.777672"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1146\/annurev.immunol.21.120601.141011","article-title":"IgA Fc receptors","volume":"21","author":"Monteiro","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.47665\/tb.41.1.014","article-title":"Impact of elevated IgE in protective immunity and immunopathology of dengue","volume":"41","author":"Annsley","year":"2024","journal-title":"Trop. Biomed."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1007\/s00018-015-1870-x","article-title":"The role of Fc\u03b5RI expressed in dendritic cells and monocytes","volume":"72","author":"Shin","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49S","DOI":"10.1111\/1523-1747.ep12875051","article-title":"Fc receptors for IgE and interleukin-4 induced IgE and IgG4 secretion","volume":"94","author":"Spiegelberg","year":"1990","journal-title":"J. Investig. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1369\/0022155417705095","article-title":"Distribution of FcRn Across Species and Tissues","volume":"65","author":"Latvala","year":"2017","journal-title":"J. Histochem. Cytochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1093\/infdis\/131.Supplement.S62","article-title":"Placental passage of antibodies to Dengue virus in persons living in a region of hyperendemic Dengue virus infection","volume":"131","author":"Ventura","year":"1975","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1080\/14787210.2017.1254550","article-title":"The mechanistic role of antibodies to dengue virus in protection and disease pathogenesis","volume":"15","author":"Gan","year":"2017","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1080\/08820139.2020.1775643","article-title":"Immunological Role of IgG Subclasses","volume":"50","author":"Napodano","year":"2021","journal-title":"Immunol. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gebo, C., Hardy, C.S.C., McElvany, B.D., Graham, N.R., Lu, J.Q., Moradpour, S., Currier, J.R., Friberg, H., Gromowski, G.D., and Thomas, S.J. (2024). B cell receptor dependent enhancement of dengue virus infection. PLoS Pathog., 20.","DOI":"10.1101\/2024.06.27.601099"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1126\/science.aal4365","article-title":"Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity","volume":"356","author":"Bardina","year":"2017","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/infdis\/jiy482","article-title":"Dengue Virus and Zika Virus Serological Cross-reactivity and Their Impact on Pathogenesis in Mice","volume":"219","author":"Watanabe","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"199376","DOI":"10.1016\/j.virusres.2024.199376","article-title":"Japanese encephalitis virus E protein domain III immunization mediates cross-protection against Zika virus in mice via antibodies and CD8(+)T cells","volume":"345","author":"Duan","year":"2024","journal-title":"Virus Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"109308","DOI":"10.1016\/j.intimp.2022.109308","article-title":"Evaluation of Zika virus DNA vaccines based on NS1 and domain III of E","volume":"113","author":"Xiong","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1021\/acs.bioconjchem.0c00700","article-title":"Conjugation of Hemoglobin and Mannan Markedly Improves the Immunogenicity of Domain III of the Zika Virus E Protein: Structural and Immunological Study","volume":"32","author":"Qi","year":"2021","journal-title":"Bioconjugate Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e0244021","DOI":"10.1128\/mBio.02440-21","article-title":"Human Monoclonal Antibodies against NS1 Protein Protect against Lethal West Nile Virus Infection","volume":"12","author":"Wessel","year":"2021","journal-title":"mBio"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Keyt, B.A., Baliga, R., Sinclair, A.M., Carroll, S.F., and Peterson, M.S. (2020). Structure, Function, and Therapeutic Use of IgM Antibodies. Antibodies, 9.","DOI":"10.3390\/antib9040053"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1084\/jem.20091107","article-title":"Identity of the elusive IgM Fc receptor (FcmuR) in humans","volume":"206","author":"Kubagawa","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"106078","DOI":"10.1016\/j.antiviral.2025.106078","article-title":"Development and optimization of an mRNA-vectored single-chain IgA1 isotype monoclonal antibody with potential to treat or prevent dengue virus infection","volume":"234","author":"Nguyen","year":"2025","journal-title":"Antivir. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"481","DOI":"10.47665\/tb.41.4.009","article-title":"Association of total and dengue-specific IgE levels in the sera with dengue virus inhibition and antibody-dependent enhancement","volume":"41","author":"Annsley","year":"2024","journal-title":"Trop. Biomed."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"eadx7231","DOI":"10.1126\/scitranslmed.adx7231","article-title":"Afucosylation of anti-dengue IgG is associated with enhanced susceptibility to dengue virus infection postvaccination","volume":"17","author":"Ashraf","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/s41564-023-01421-y","article-title":"Human Fc\u03b3RIIIa activation on splenic macrophages drives dengue pathogenesis in mice","volume":"8","author":"Yamin","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Golay, J., Andrea, A.E., and Cattaneo, I. (2022). Role of Fc Core Fucosylation in the Effector Function of IgG1 Antibodies. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.929895"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/glycob\/cwaa018","article-title":"Understanding the role of antibody glycosylation through the lens of severe viral and bacterial diseases","volume":"30","author":"Irvine","year":"2020","journal-title":"Glycobiology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yang, M., Sun, H., Lai, H., Neupane, B., Bai, F., Steinkellner, H., and Chen, Q. (2023). Plant-Produced Anti-Zika Virus Monoclonal Antibody Glycovariant Exhibits Abrogated Antibody-Dependent Enhancement of Infection. Vaccines, 11.","DOI":"10.3390\/vaccines11040755"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sun, H., Yang, M., Lai, H., Neupane, B., Teh, A.Y., Jugler, C., Ma, J.K., Steinkellner, H., Bai, F., and Chen, Q. (2023). A Dual-Approach Strategy to Optimize the Safety and Efficacy of Anti-Zika Virus Monoclonal Antibody Therapeutics. Viruses, 15.","DOI":"10.3390\/v15051156"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12987","DOI":"10.1038\/s41598-021-92403-9","article-title":"An affinity-matured human monoclonal antibody targeting fusion loop epitope of dengue virus with in vivo therapeutic potency","volume":"11","author":"Kotaki","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e0142924","DOI":"10.1128\/jvi.01429-24","article-title":"Protective threshold of a potent neutralizing Zika virus monoclonal antibody in rhesus macaques","volume":"98","author":"Nkolola","year":"2024","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.virol.2022.09.007","article-title":"A human monoclonal antibody to neutralize all four serotypes of dengue virus derived from patients at the convalescent phase of infection","volume":"576","author":"Lu","year":"2022","journal-title":"Virology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1126\/science.abc7303","article-title":"Antibody fucosylation predicts disease severity in secondary dengue infection","volume":"372","author":"Bournazos","year":"2021","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nri1266","article-title":"Human antibody-Fc receptor interactions illuminated by crystal structures","volume":"4","author":"Woof","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41577-020-00410-0","article-title":"The role of IgG Fc receptors in antibody-dependent enhancement","volume":"20","author":"Bournazos","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10128","DOI":"10.1128\/JVI.00792-06","article-title":"Differential enhancement of dengue virus immune complex infectivity mediated by signaling-competent and signaling-incompetent human Fcgamma RIA (CD64) or FcgammaRIIA (CD32)","volume":"80","author":"Rodrigo","year":"2006","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e0158224","DOI":"10.1128\/jvi.01582-24","article-title":"Functional genomics screens reveal a role for TBC1D24 and SV2B in antibody-dependent enhancement of dengue virus infection","volume":"98","author":"Belmont","year":"2024","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12479","DOI":"10.1073\/pnas.1106568108","article-title":"Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection","volume":"108","author":"Chan","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Breedveld, A., and van Egmond, M. (2019). IgA and Fc\u03b1RI: Pathological Roles and Therapeutic Opportunities. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00553"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"691","DOI":"10.4269\/ajtmh.15-0199","article-title":"Association of Fc\u03b3RIIa Polymorphism with Clinical Outcome of Dengue Infection: First Insight from Pakistan","volume":"93","author":"Mohsin","year":"2015","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.4269\/ajtmh.2010.09-0353","article-title":"Asymptomatic dengue infection in a Cuban population confirms the protective role of the RR variant of the FcgammaRIIa polymorphism","volume":"82","author":"Sierra","year":"2010","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"102","DOI":"10.4269\/ajtmh.2002.67.102","article-title":"Susceptibility to dengue hemorrhagic fever in vietnam: Evidence of an association with variation in the vitamin d receptor and Fc gamma receptor IIa genes","volume":"67","author":"Loke","year":"2002","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.actatropica.2014.05.021","article-title":"Contrasting associations of polymorphisms in Fc\u03b3RIIa and DC-SIGN with the clinical presentation of dengue infection in a Mexican population","volume":"138","author":"Noecker","year":"2014","journal-title":"Acta Trop."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e46689","DOI":"10.7554\/eLife.46689","article-title":"Fc\u03b3RIIB-I232T polymorphic change allosterically suppresses ligand binding","volume":"8","author":"Hu","year":"2019","journal-title":"eLife"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12111","DOI":"10.1016\/S0021-9258(17)32688-1","article-title":"Clustering of the high affinity Fc receptor for immunoglobulin G (Fc gamma RI) results in phosphorylation of its associated gamma-chain","volume":"269","author":"Duchemin","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.1016\/S0021-9258(17)37549-X","article-title":"Differential control of the tyrosine kinases Lyn and Syk by the two signaling chains of the high affinity immunoglobulin E receptor","volume":"269","author":"Jouvin","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6794","DOI":"10.4049\/jimmunol.151.12.6794","article-title":"Fc gamma RIIIA-mediated signaling involves src-family lck in human natural killer cells","volume":"151","author":"Pignata","year":"1993","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"17306","DOI":"10.1074\/jbc.M115.664136","article-title":"Spleen Tyrosine Kinase (Syk) Mediates IL-1\u03b2 Induction by Primary Human Monocytes during Antibody-enhanced Dengue Virus Infection","volume":"290","author":"Callaway","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1097\/01.ASN.0000113241.98702.77","article-title":"Activation of Syk in neutrophils by antineutrophil cytoplasm antibodies occurs via Fcgamma receptors and CD18","volume":"15","author":"Hewins","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1146\/annurev.immunol.021908.132706","article-title":"T cell activation","volume":"27","author":"Koretzky","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1016\/j.bpj.2024.01.036","article-title":"Antibody surface mobility amplifies Fc\u03b3R signaling via Arp2\/3 during phagocytosis","volume":"123","author":"Jo","year":"2024","journal-title":"Biophys. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nri2765","article-title":"The SYK tyrosine kinase: A crucial player in diverse biological functions","volume":"10","author":"Ruland","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.cyto.2004.10.009","article-title":"Interleukin-1 stimulates cytokines, prostaglandin E2 and matrix metalloproteinase-1 production via activation of MAPK\/AP-1 and NF-kappaB in human gingival fibroblasts","volume":"29","author":"Kida","year":"2005","journal-title":"Cytokine"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0165-6147(97)90657-X","article-title":"Tumour necrosis factor alpha and interleukin 1 signalling: Do MAPKK kinases connect it all?","volume":"18","author":"Eder","year":"1997","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1002\/eji.1830270825","article-title":"Differential association of phosphatases with hematopoietic co-receptors bearing immunoreceptor tyrosine-based inhibition motifs","volume":"27","author":"Olivero","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/383263a0","article-title":"Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB","volume":"383","author":"Ono","year":"1996","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/1096-9071(20000201)63:2<150::AID-JMV1010>3.0.CO;2-A","article-title":"Antibody-dependent enhancement of heterotypic dengue infections involved in suppression of IFNgamma production","volume":"63","author":"Yang","year":"2001","journal-title":"J. Med. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1099\/vir.0.82537-0","article-title":"Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-inflammatory cytokine production, in THP-1 cells","volume":"88","author":"Chareonsirisuthigul","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1086\/651018","article-title":"Mechanisms of immune evasion induced by a complex of dengue virus and preexisting enhancing antibodies","volume":"201","author":"Ubol","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e0196224","DOI":"10.1128\/jvi.01962-24","article-title":"Conventional and antibody-enhanced DENV infection of human macrophages induces differential immunotranscriptomic profiles","volume":"99","author":"Hardy","year":"2025","journal-title":"J. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e0177222","DOI":"10.1128\/spectrum.01772-22","article-title":"Zika Virus Replication in a Mast Cell Model is Augmented by Dengue Virus Antibody-Dependent Enhancement and Features a Selective Immune Mediator Secretory Profile","volume":"10","author":"Coish","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.chom.2007.09.015","article-title":"Complement protein C1q inhibits antibody-dependent enhancement of flavivirus infection in an IgG subclass-specific manner","volume":"2","author":"Mehlhop","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1002\/1873-3468.13730","article-title":"Dengue virus and the complement alternative pathway","volume":"594","author":"Carr","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.virusres.2013.11.007","article-title":"C1q binding to dengue virus decreases levels of infection and inflammatory molecules transcription in THP-1 cells","volume":"179","author":"Douradinha","year":"2014","journal-title":"Virus Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.chom.2010.07.007","article-title":"Direct complement restriction of flavivirus infection requires glycan recognition by mannose-binding lectin","volume":"8","author":"Fuchs","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"I100","DOI":"10.1016\/j.vaccine.2008.11.061","article-title":"Complement and its role in protection and pathogenesis of flavivirus infections","volume":"26","author":"Avirutnan","year":"2008","journal-title":"Vaccine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.molimm.2022.11.010","article-title":"Antibody-Dependent Enhancement (ADE) and the role of complement system in disease pathogenesis","volume":"152","author":"Thomas","year":"2022","journal-title":"Mol. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1128\/JVI.00992-07","article-title":"Infection-enhancing and -neutralizing activities of mouse monoclonal antibodies against dengue type 2 and 4 viruses are controlled by complement levels","volume":"82","author":"Yamanaka","year":"2008","journal-title":"J. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.chom.2009.09.003","article-title":"Complement protein C1q reduces the stoichiometric threshold for antibody-mediated neutralization of West Nile virus","volume":"6","author":"Mehlhop","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.ijid.2020.12.039","article-title":"Role of the complement system in antibody-dependent enhancement of flavivirus infections","volume":"103","author":"Byrne","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2471035","DOI":"10.1080\/22221751.2025.2471035","article-title":"Lessons for medical countermeasure development from unforeseen outbreaks","volume":"14","author":"Mura","year":"2025","journal-title":"Emerg. Microbes Infect."},{"key":"ref_89","unstructured":"Centers for Disease Control and Prevention (2026, August 17). Dengue Vaccine, Available online: https:\/\/www.cdc.gov\/dengue\/hcp\/vaccine\/index.html."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1021\/acs.jmedchem.9b00775","article-title":"Drugs for the Treatment of Zika Virus Infection","volume":"63","author":"Bernatchez","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_91","unstructured":"Infectious Diseases Clinical Research Consortium (IDCRC) (2026, August 17). IDCRC Launches Clinical Trial to Study the Safety and Immunogenicity of an Inactivated West Nile Virus Vaccine. Available online: https:\/\/idcrc.org\/about\/news-archive\/west-nile.html."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"11558","DOI":"10.1038\/s41467-025-67447-4","article-title":"Rational design of flavivirus E protein vaccine optimizes immunogenicity and mitigates antibody dependent enhancement risk","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"112534","DOI":"10.1016\/j.isci.2025.112534","article-title":"A two-component cocktail of engineered DIII nanoparticles elicits broadly neutralizing antibody responses against dengue virus in mice","volume":"28","author":"Mariano","year":"2025","journal-title":"iScience"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"8932","DOI":"10.1038\/s41467-024-53242-0","article-title":"A single-dose circular RNA vaccine prevents Zika virus infection without enhancing dengue severity in mice","volume":"15","author":"Liu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Parra-Gonz\u00e1lez, M., N\u00e1jera-Maldonado, L., Peralta-Cuevas, E., Gutierrez-Onofre, A.J., Garcia-Atutxa, I., and Villanueva-Flores, F. (2025). Overcoming dengue vaccine challenges through next-generation virus-like particle immunization strategies. Front. Cell Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1614805"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2557097","DOI":"10.1080\/21645515.2025.2557097","article-title":"Identification of multifunctional T-cell peptide epitopes for the development of DNA vaccines against dengue virus","volume":"21","author":"Sun","year":"2025","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Su, H., Liu, J., Yu, J., Qiu, Z., Liang, W., Wu, W., Mo, H., Li, H., Zhao, W., and Gu, W. (2023). EDIII-Fc induces protective immune responses against the Zika virus in mice and rhesus macaque. PLoS Negl. Trop. Dis., 17.","DOI":"10.1371\/journal.pntd.0011770"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Karkashan, A. (2024). Immunoinformatics assisted profiling of West Nile virus proteome to determine immunodominant epitopes for the development of next-generation multi-peptide vaccine. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1395870"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Sun, H., Acharya, D., Paul, A.M., Lai, H., He, J., Bai, F., and Chen, Q. (2023). Antibody-Dependent Enhancement Activity of a Plant-Made Vaccine against West Nile Virus. Vaccines, 11.","DOI":"10.3390\/vaccines11020197"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12977-017-0380-3","article-title":"Systems serology: Profiling vaccine induced humoral immunity against HIV","volume":"14","author":"Chung","year":"2017","journal-title":"Retrovirology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jim.2018.01.013","article-title":"Optimization and qualification of an Fc Array assay for assessments of antibodies against HIV-1\/SIV","volume":"455","author":"Brown","year":"2018","journal-title":"J. Immunol. Methods"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.virs.2025.11.009","article-title":"Antiviral agents for dengue virus","volume":"40","author":"Jiang","year":"2025","journal-title":"Virol. Sin."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s00284-020-02284-w","article-title":"Current Understanding of the Pathogenesis of Dengue Virus Infection","volume":"78","author":"Bhatt","year":"2021","journal-title":"Curr. Microbiol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"6004","DOI":"10.1016\/j.vaccine.2022.09.012","article-title":"Engineered flavivirus vaccines control induction of crossreactive infection-enhancing and -neutralizing antibodies","volume":"40","author":"Yamanaka","year":"2022","journal-title":"Vaccine"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Sarker, A., Dhama, N., and Gupta, R.D. (2023). Dengue virus neutralizing antibody: A review of targets, cross-reactivity, and antibody-dependent enhancement. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1200195"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e20329","DOI":"10.7717\/peerj.20329","article-title":"Dissecting antibody-dependent enhancement modulation by Fc-modified cross-neutralizing human monoclonal antibody","volume":"13","author":"Injampa","year":"2025","journal-title":"PeerJ"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Hu, D., Zhu, Z., Li, S., Deng, Y., Wu, Y., Zhang, N., Puri, V., Wang, C., Zou, P., and Lei, C. (2019). A broadly neutralizing germline-like human monoclonal antibody against dengue virus envelope domain III. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007836"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7981","DOI":"10.1073\/pnas.2000414117","article-title":"A combination of two human monoclonal antibodies limits fetal damage by Zika virus in macaques","volume":"117","author":"Coffey","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Slon Campos, J.L., Poggianella, M., Marchese, S., Mossenta, M., Rana, J., Arnoldi, F., Bestagno, M., and Burrone, O.R. (2017). DNA-immunisation with dengue virus E protein domains I\/II, but not domain III, enhances Zika, West Nile and Yellow Fever virus infection. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181734"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.4049\/jimmunol.1700029","article-title":"Antibody Epitopes Identified in Critical Regions of Dengue Virus Nonstructural 1 Protein in Mouse Vaccination and Natural Human Infections","volume":"198","author":"Hertz","year":"2017","journal-title":"J. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"9331","DOI":"10.1039\/C9SC03840J","article-title":"Site-specific C-terminal dinitrophenylation to reconstitute the antibody Fc functions for nanobodies","volume":"10","author":"Hong","year":"2019","journal-title":"Chem. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"719","DOI":"10.7150\/ijms.5037","article-title":"Inhibition of dengue virus entry into target cells using synthetic antiviral peptides","volume":"10","author":"Alhoot","year":"2013","journal-title":"Int. J. Med. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/cbdd.12576","article-title":"A peptide inhibitor derived from the conserved ectodomain region of DENV membrane (M) protein with activity against dengue virus infection","volume":"86","author":"Panya","year":"2015","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Panya, A., Songprakhon, P., Panwong, S., Jantakee, K., Kaewkod, T., Tragoolpua, Y., Sawasdee, N., Lee, V.S., Nimmanpipug, P., and Yenchitsomanus, P.T. (2021). Cordycepin Inhibits Virus Replication in Dengue Virus-Infected Vero Cells. Molecules, 26.","DOI":"10.3390\/molecules26113118"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Ratanakomol, T., Roytrakul, S., Wikan, N., and Smith, D.R. (2021). Berberine Inhibits Dengue Virus through Dual Mechanisms. Molecules, 26.","DOI":"10.3390\/molecules26185501"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/s41586-021-03990-6","article-title":"A pan-serotype dengue virus inhibitor targeting the NS3-NS4B interaction","volume":"598","author":"Kaptein","year":"2021","journal-title":"Nature"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6345","DOI":"10.1038\/s41598-017-06612-2","article-title":"Evaluation of Sofosbuvir (\u03b2-D-2\u2032-deoxy-2\u2032-\u03b1-fluoro-2\u2032-\u03b2-C-methyluridine) as an inhibitor of Dengue virus replication","volume":"7","author":"Xu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.antiviral.2015.10.012","article-title":"Antibody with an engineered Fc region as a therapeutic agent against dengue virus infection","volume":"124","author":"Ramadhany","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/nrd.2017.33","article-title":"Broad-spectrum agents for flaviviral infections: Dengue, Zika and beyond","volume":"16","author":"Boldescu","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Shimizu, H., Saito, A., Mikuni, J., Nakayama, E.E., Koyama, H., Honma, T., Shirouzu, M., Sekine, S.I., and Shioda, T. (2019). Discovery of a small molecule inhibitor targeting dengue virus NS5 RNA-dependent RNA polymerase. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007894"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/916\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T13:00:30Z","timestamp":1787230830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":120,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["v18080916"],"URL":"https:\/\/doi.org\/10.3390\/v18080916","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}