An in-depth analysis of original antigenic sin in dengue virus infection
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 freq...
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th-mahidol.113892018-05-03T15:18:13Z An in-depth analysis of original antigenic sin in dengue virus infection 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 Gavin R. Screaton Imperial College London Khon Kaen Regional Hospital Songkhla Hospital UCL Wellcome Trust Centre for Human Genetics Mahidol University Thailand National Center for Genetic Engineering and Biotechnology Agricultural and Biological Sciences Immunology and Microbiology 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. Copyright © 2011, American Society for Microbiology. All Rights Reserved. 2018-05-03T07:58:10Z 2018-05-03T07:58:10Z 2011-01-01 Article Journal of Virology. Vol.85, No.1 (2011), 410-421 10.1128/JVI.01826-10 10985514 0022538X 2-s2.0-78650069522 https://repository.li.mahidol.ac.th/handle/123456789/11389 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=78650069522&origin=inward |
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Agricultural and Biological Sciences Immunology and Microbiology 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 Gavin R. Screaton An in-depth analysis of original antigenic sin in dengue virus infection |
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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. Copyright © 2011, American Society for Microbiology. All Rights Reserved. |
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Imperial College London |
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Imperial College London 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 Gavin R. Screaton |
format |
Article |
author |
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 Gavin R. Screaton |
author_sort |
Claire M. Midgley |
title |
An in-depth analysis of original antigenic sin in dengue virus infection |
title_short |
An in-depth analysis of original antigenic sin in dengue virus infection |
title_full |
An in-depth analysis of original antigenic sin in dengue virus infection |
title_fullStr |
An in-depth analysis of original antigenic sin in dengue virus infection |
title_full_unstemmed |
An in-depth analysis of original antigenic sin in dengue virus infection |
title_sort |
in-depth analysis of original antigenic sin in dengue virus infection |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/11389 |
_version_ |
1763488206105346048 |