ATTENUATION BIOMARKERS OF DENGUE 4 VIRUS STRAIN 1036 PDK40 INFECTIOUS CLONE
Jundee Rabablert1, Supoth Rajakam2, Kumchol Chaiyo1,2 and Sutee Yoksan2,3
Keywords:
dengue, vaccine, dengue virus, Gibson assembly, infectious clone, live attenuated vaccineAbstract
Dengue viruses (DENV) transmitted by Aedes mosquitoes cause hemorrhagic fever and shock syndrome in tropical and subtropical regions. Live-attenuated (LAV) DEN4V 1036 PDK40 showed small plaque size in LLC-MK2 cells at 37ºC, but not at 39.4ºC and produced low neurovirulence in suckling mice. The major limitations of LAV are genetic instability and reversion. In order to expand the tools available for dengue vaccine development, an infectious clone (IC) DEN4V 1036 PDK40 was constructed from LAV DEN4V 1036 PDK40. IC-DEN4V-1036-PDK40 demonstrated attenuated characteristics, namely, small/pinpoint plaque sizes, temperature sensitivity, low growth efficiency in Ae. aegypti, and low neurovirulence in suckling mice. These results indicate IC-DEN4V-1036-PDK40 fulfilled all in vitro and in vivo safety requirements and should be useful for development as a dengue or a backbone for Flavivirus-chimeric vaccines.
Published
Versions
- 2021-03-11 (2)
- 2020-05-19 (1)