Dengue virus and host antibody: a dangerous balancing act

Lidbury, Brett A.; Mahalingam, Suresh

doi:10.1016/s1473-3099(14)70843-6

Cited by 2 publications

(2 citation statements)

References 12 publications

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“…HuH-7 and Raji cells stably expressing DC-SIGN (gift from Timothy Burgess 20 36 ) were cultured in Dulbecco’s Modified Essential Medium (DMEM) while THP-1 and BHK21 cells were cultured in RPMI Medium 1640 (Gibco) supplemented with 10% foetal calf serum. Primary human monocytes were derived from blood obtained from the principal investigator using a protocol previously described 37 . DENV strains of the original Mahidol stocks (DENV-2 16681, DENV-2 PDK53, DENV-3 16562 and DENV-3 PGMK30FRhL3) were obtained from Dr Claire Huang (Centers for Disease Control and Prevention, USA) and were passaged three times in C6/36 cells in our laboratory.…”

Section: Methodsmentioning

confidence: 99%

Molecular determinants of plaque size as an indicator of dengue virus attenuation

Goh

Tang

Norton

et al. 2016

Sci Rep

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The development of live viral vaccines relies on empirically derived phenotypic criteria, especially small plaque sizes, to indicate attenuation. However, while some candidate vaccines successfully translated into licensed applications, others have failed safety trials, placing vaccine development on a hit-or-miss trajectory. We examined the determinants of small plaque phenotype in two dengue virus (DENV) vaccine candidates, DENV-3 PGMK30FRhL3, which produced acute febrile illness in vaccine recipients, and DENV-2 PDK53, which has a good clinical safety profile. The reasons behind the failure of PGMK30FRhL3 during phase 1 clinical trial, despite meeting the empirically derived criteria of attenuation, have never been systematically investigated. Using in vitro, in vivo and functional genomics approaches, we examined infections by the vaccine and wild-type DENVs, in order to ascertain the different determinants of plaque size. We show that PGMK30FRhL3 produces small plaques on BHK-21 cells due to its slow in vitro growth rate. In contrast, PDK53 replicates rapidly, but is unable to evade antiviral responses that constrain its spread hence also giving rise to small plaques. Therefore, at least two different molecular mechanisms govern the plaque phenotype; determining which mechanism operates to constrain plaque size may be more informative on the safety of live-attenuated vaccines.

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Section: Methodsmentioning

confidence: 99%

Molecular determinants of plaque size as an indicator of dengue virus attenuation

Goh

Tang

Norton

et al. 2016

Sci Rep

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show abstract

“…In addition, concern has been expressed about the antibody-dependent enhancement (ADE) of dengue virus in individuals exposed to natural infection, with its association with complications like Dengue Shock Syndrome and Dengue Hemorrhagic Fever. 11 These issues need to be factored while developing a dengue vaccine.…”

Section: Immunity and Vaccine Developmentmentioning

confidence: 99%

Dengue: A runaway epidemic and a bewildered public health worker

Mukherji

Kaushik

2015

Medical Journal Armed Forces India

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Dengue virus and host antibody: a dangerous balancing act

Cited by 2 publications

References 12 publications

Molecular determinants of plaque size as an indicator of dengue virus attenuation

Molecular determinants of plaque size as an indicator of dengue virus attenuation

Dengue: A runaway epidemic and a bewildered public health worker

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