20980526
not annotated - annotated - LINNAEUS only
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 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.
Ann file
T1 Species 50 62 dengue virus
N1 Reference T1 Taxonomy:12637
T2 Species 92 106 dengue viruses
N2 Reference T2 Taxonomy:12637
T3 Species 395 401 Dengue
N3 Reference T3 Taxonomy:12637
T4 Species 451 457 dengue
N4 Reference T4 Taxonomy:12637
T5 Species 545 551 dengue
N5 Reference T5 Taxonomy:12637
T6 Species 855 867 dengue virus
N6 Reference T6 Taxonomy:12637
T7 Species 1214 1220 dengue
N7 Reference T7 Taxonomy:12637
T8 Species 1405 1411 dengue
N8 Reference T8 Taxonomy:12637
T9 Species 1661 1667 dengue
N9 Reference T9 Taxonomy:12637
T10 Species 1691 1697 dengue
N10 Reference T10 Taxonomy:12637
T11 Species 702 708 dengue
N11 Reference T11 Taxonomy:12637