Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/72978
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Type: Journal article
Title: An in-depth analysis of original antigenic sin in dengue virus infection
Author: Midgley, C.
Bajwa-Joseph, M.
Vasanawathana, S.
Limpitikul, W.
Wills, B.
Flanagan, A.
Waiyaiya, E.
Tran, H.
Cowper, A.
Chotiyarnwon, P.
Grimes, J.
Yoksan, S.
Malasit, P.
Simmons, C.
Mongkolsapaya, J.
Screaton, G.
Citation: Journal of Virology, 2011; 85(1):410-421
Publisher: Amer Soc Microbiology
Issue Date: 2011
ISSN: 0022-538X
1098-5514
Statement of
Responsibility: 
Claire 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
Abstract: The 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.
Keywords: Monocytes; U937 Cells; Humans; Dengue Virus; Dengue; Viral Envelope Proteins; Antibodies, Viral; Antigens, Viral; Enzyme-Linked Immunosorbent Assay; Neutralization Tests; Serotyping; Antibody Affinity; Cross Reactions; Child; Child, Preschool; Female; Male; Dengue Vaccines; Severe Dengue
Rights: Copyright © 2011, American Society for Microbiology. All Rights Reserved.
RMID: 0020111710
DOI: 10.1128/JVI.01826-10
Appears in Collections:Medicine publications

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