BACKGROUND: Infection with any 1 of the 4 dengue viruses (DVs) can produce several illnesses, ranging from a mild febrile illness to classic dengue fever (DF) to dengue hemorrhagic fever (DHF), a potentially life-threatening disease. Most DHF cases occur after sequential heterotypic DV infections. The role of preexisting humoral immunity in modifying severity of dengue disease is not well understood. METHODS: We conducted a prospective cohort study of children in a region where dengue disease is hyperendemic and examined the role of preexisting neutralizing anti-DV antibodies (Abs) in modifying secondary dengue-3 virus (D3V), dengue-2 virus (D2V), and dengue-1 virus (D1V) infections. RESULTS: In secondary D3V infection, higher levels of preexisting neutralizing Ab directed against D3V (reference virus strain and patient's virus isolate) were associated with lower viremia levels and milder disease. Preexisting neutralizing Ab levels against D2V were not associated with severity of secondary D2V infection. The levels of preexisting neutralizing Ab against the infecting virus isolates were not associated with viremia levels in secondary D2V or D1V infections. CONCLUSIONS: Cross-reactive memory humoral immune responses appear to be beneficial in symptomatic secondary D3V infection, but not in secondary D2V or D1V infection. These results may have important implications for the development of live attenuated tetravalent dengue vaccines.
BACKGROUND:Infection with any 1 of the 4 dengue viruses (DVs) can produce several illnesses, ranging from a mild febrile illness to classic dengue fever (DF) to dengue hemorrhagic fever (DHF), a potentially life-threatening disease. Most DHF cases occur after sequential heterotypic DV infections. The role of preexisting humoral immunity in modifying severity of dengue disease is not well understood. METHODS: We conducted a prospective cohort study of children in a region where dengue disease is hyperendemic and examined the role of preexisting neutralizing anti-DV antibodies (Abs) in modifying secondary dengue-3 virus (D3V), dengue-2 virus (D2V), and dengue-1 virus (D1V) infections. RESULTS: In secondary D3V infection, higher levels of preexisting neutralizing Ab directed against D3V (reference virus strain and patient's virus isolate) were associated with lower viremia levels and milder disease. Preexisting neutralizing Ab levels against D2V were not associated with severity of secondary D2V infection. The levels of preexisting neutralizing Ab against the infecting virus isolates were not associated with viremia levels in secondary D2V or D1V infections. CONCLUSIONS: Cross-reactive memory humoral immune responses appear to be beneficial in symptomatic secondary D3V infection, but not in secondary D2V or D1Vinfection. These results may have important implications for the development of live attenuated tetravalent dengue vaccines.
Authors: Anuja Mathew; Kim West; Siripen Kalayanarooj; Robert V Gibbons; Anon Srikiatkhachorn; Sharone Green; Daniel Libraty; Smita Jaiswal; Alan L Rothman Journal: J Infect Dis Date: 2011-09-19 Impact factor: 5.226
Authors: Katherine L Williams; Wahala M P B Wahala; Susana Orozco; Aravinda M de Silva; Eva Harris Journal: Virology Date: 2012-04-25 Impact factor: 3.616
Authors: Leah C Katzelnick; Magelda Montoya; Lionel Gresh; Angel Balmaseda; Eva Harris Journal: Proc Natl Acad Sci U S A Date: 2016-01-04 Impact factor: 11.205
Authors: Leah C Katzelnick; Judith M Fonville; Gregory D Gromowski; Jose Bustos Arriaga; Angela Green; Sarah L James; Louis Lau; Magelda Montoya; Chunling Wang; Laura A VanBlargan; Colin A Russell; Hlaing Myat Thu; Theodore C Pierson; Philippe Buchy; John G Aaskov; Jorge L Muñoz-Jordán; Nikos Vasilakis; Robert V Gibbons; Robert B Tesh; Albert D M E Osterhaus; Ron A M Fouchier; Anna Durbin; Cameron P Simmons; Edward C Holmes; Eva Harris; Stephen S Whitehead; Derek J Smith Journal: Science Date: 2015-09-18 Impact factor: 47.728