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...
| Prif Awduron: | , , , , , , , , , , , , , , , , |
|---|---|
| Fformat: | Journal article |
| Iaith: | English |
| Cyhoeddwyd: |
2011
|
| _version_ | 1826271446432743424 |
|---|---|
| author | Midgley, C Bajwa-Joseph, M Vasanawathana, S Limpitikul, W Wills, B Flanagan, A Waiyaiya, E Tran, H Cowper, A Chotiyarnwong, P Chotiyarnwon, P Grimes, J Yoksan, S Malasit, P Simmons, C Mongkolsapaya, J Screaton, G |
| author_facet | Midgley, C Bajwa-Joseph, M Vasanawathana, S Limpitikul, W Wills, B Flanagan, A Waiyaiya, E Tran, H Cowper, A Chotiyarnwong, P Chotiyarnwon, P Grimes, J Yoksan, S Malasit, P Simmons, C Mongkolsapaya, J Screaton, G |
| author_sort | Midgley, C |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:56:47Z |
| format | Journal article |
| id | oxford-uuid:4d2ea2e4-9a98-4a2f-acfc-8dcb1106fec3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:56:47Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:4d2ea2e4-9a98-4a2f-acfc-8dcb1106fec32022-03-26T15:54:00ZAn in-depth analysis of original antigenic sin in dengue virus infection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4d2ea2e4-9a98-4a2f-acfc-8dcb1106fec3EnglishSymplectic Elements at Oxford2011Midgley, CBajwa-Joseph, MVasanawathana, SLimpitikul, WWills, BFlanagan, AWaiyaiya, ETran, HCowper, AChotiyarnwong, PChotiyarnwon, PGrimes, JYoksan, SMalasit, PSimmons, CMongkolsapaya, JScreaton, GThe 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. |
| spellingShingle | Midgley, C Bajwa-Joseph, M Vasanawathana, S Limpitikul, W Wills, B Flanagan, A Waiyaiya, E Tran, H Cowper, A Chotiyarnwong, P Chotiyarnwon, P Grimes, J Yoksan, S Malasit, P Simmons, C Mongkolsapaya, J Screaton, G An in-depth analysis of original antigenic sin in dengue virus infection. |
| title | 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_short | 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 |
| work_keys_str_mv | AT midgleyc anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT bajwajosephm anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT vasanawathanas anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT limpitikulw anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT willsb anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT flanagana anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT waiyaiyae anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT tranh anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT cowpera anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT chotiyarnwongp anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT chotiyarnwonp anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT grimesj anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT yoksans anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT malasitp anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT simmonsc anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT mongkolsapayaj anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT screatong anindepthanalysisoforiginalantigenicsinindenguevirusinfection AT midgleyc indepthanalysisoforiginalantigenicsinindenguevirusinfection AT bajwajosephm indepthanalysisoforiginalantigenicsinindenguevirusinfection AT vasanawathanas indepthanalysisoforiginalantigenicsinindenguevirusinfection AT limpitikulw indepthanalysisoforiginalantigenicsinindenguevirusinfection AT willsb indepthanalysisoforiginalantigenicsinindenguevirusinfection AT flanagana indepthanalysisoforiginalantigenicsinindenguevirusinfection AT waiyaiyae indepthanalysisoforiginalantigenicsinindenguevirusinfection AT tranh indepthanalysisoforiginalantigenicsinindenguevirusinfection AT cowpera indepthanalysisoforiginalantigenicsinindenguevirusinfection AT chotiyarnwongp indepthanalysisoforiginalantigenicsinindenguevirusinfection AT chotiyarnwonp indepthanalysisoforiginalantigenicsinindenguevirusinfection AT grimesj indepthanalysisoforiginalantigenicsinindenguevirusinfection AT yoksans indepthanalysisoforiginalantigenicsinindenguevirusinfection AT malasitp indepthanalysisoforiginalantigenicsinindenguevirusinfection AT simmonsc indepthanalysisoforiginalantigenicsinindenguevirusinfection AT mongkolsapayaj indepthanalysisoforiginalantigenicsinindenguevirusinfection AT screatong indepthanalysisoforiginalantigenicsinindenguevirusinfection |