title: An in-depth analysis of original antigenic sin in dengue virus infection.
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.
authors.affiliation: Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London, United Kingdom.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Midgley
authors.forename: Martha
authors.initials: M
authors.lastname: Bajwa-Joseph
authors.forename: Sirijitt
authors.initials: S
authors.lastname: Vasanawathana
authors.forename: Wannee
authors.initials: W
authors.lastname: Limpitikul
authors.forename: Bridget
authors.initials: B
authors.lastname: Wills
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Flanagan
authors.forename: Emily
authors.initials: E
authors.lastname: Waiyaiya
authors.forename: Hai Bac
authors.initials: HB
authors.lastname: Tran
authors.forename: Alison E
authors.initials: AE
authors.lastname: Cowper
authors.forename: Pojchong
authors.initials: P
authors.lastname: Chotiyarnwong
authors.forename: Pojchong
authors.initials: P
authors.lastname: Chotiyarnwon
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Grimes
authors.forename: Sutee
authors.initials: S
authors.lastname: Yoksan
authors.forename: Prida
authors.initials: P
authors.lastname: Malasit
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.forename: Juthathip
authors.initials: J
authors.lastname: Mongkolsapaya
authors.forename: Gavin R
authors.initials: GR
authors.lastname: Screaton
mesh_terms: D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000915:Antibody Affinity; D000956:Antigens, Viral / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D003715:Dengue / Q000276:immunology* / Q000821:virology; D053059:Dengue Vaccines / Q000276:immunology; D003716:Dengue Virus / Q000145:classification* / Q000276:immunology* / Q000472:pathogenicity; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009000:Monocytes / Q000821:virology; D009500:Neutralization Tests; D012703:Serotyping; D019595:Severe Dengue / Q000276:immunology* / Q000821:virology; D020298:U937 Cells; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D053059:Dengue Vaccines; D014759:Viral Envelope Proteins