An in-depth analysis of original antigenic sin in dengue virus infection

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dc.contributor.authorMidgley, C.
dc.contributor.authorBajwa-Joseph, M.
dc.contributor.authorVasanawathana, S.
dc.contributor.authorLimpitikul, W.
dc.contributor.authorWills, B.
dc.contributor.authorFlanagan, A.
dc.contributor.authorWaiyaiya, E.
dc.contributor.authorTran, H.
dc.contributor.authorCowper, A.
dc.contributor.authorChotiyarnwon, P.
dc.contributor.authorGrimes, J.
dc.contributor.authorYoksan, S.
dc.contributor.authorMalasit, P.
dc.contributor.authorSimmons, C.
dc.contributor.authorMongkolsapaya, J.
dc.contributor.authorScreaton, G.
dc.date.issued2011
dc.description.abstractThe evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simple in vitro enzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.
dc.description.statementofresponsibilityClaire M. Midgley, Martha Bajwa-Joseph, Sirijitt Vasanawathana, Wannee Limpitikul, Bridget Wills, Aleksandra Flanagan, Emily Waiyaiya, Hai Bac Tran, Alison E. Cowper, Pojchong Chotiyarnwon, Jonathan M. Grimes, Sutee Yoksan, Prida Malasit, Cameron P. Simmons, Juthathip Mongkolsapaya, and Gavin R. Screaton
dc.identifier.citationJournal of Virology, 2011; 85(1):410-421
dc.identifier.doi10.1128/JVI.01826-10
dc.identifier.issn0022-538X
dc.identifier.issn1098-5514
dc.identifier.orcidTran, H. [0000-0002-9463-4033]
dc.identifier.urihttp://hdl.handle.net/2440/72978
dc.language.isoen
dc.publisherAmer Soc Microbiology
dc.rightsCopyright © 2011, American Society for Microbiology. All Rights Reserved.
dc.source.urihttps://doi.org/10.1128/jvi.01826-10
dc.subjectMonocytes
dc.subjectU937 Cells
dc.subjectHumans
dc.subjectDengue Virus
dc.subjectDengue
dc.subjectViral Envelope Proteins
dc.subjectAntibodies, Viral
dc.subjectAntigens, Viral
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectNeutralization Tests
dc.subjectSerotyping
dc.subjectAntibody Affinity
dc.subjectCross Reactions
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectFemale
dc.subjectMale
dc.subjectDengue Vaccines
dc.subjectSevere Dengue
dc.titleAn in-depth analysis of original antigenic sin in dengue virus infection
dc.typeJournal article
pubs.publication-statusPublished

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