Molecular characterization of attenuated Japanese encephalitis live vaccine strain ML-17.
The Japanese encephalitis (JE) zoonotic vaccine strain ML-17 was sequenced and compared to related JE virus strains to identify genomic attenuation markers. Relative to its parental strain, JaOH0566, 25 nucleotide alterations and 10 amino acid changes to, prM/M(2), NS2A(1), NS4B(3) and NS5(4) proteins were recorded. Both structural-gene changes were in the prM/M region (127Met-->Ile and 274Asn-->Thr). To study the effects of these prM/M changes, mutants bearing the changes were prepared using an infectious clone of JaOArS982 previously established at this lab. Compared with JaOArS982, mutant 127(Met-->Ile) showed marked reduction in murine neuroinvasiveness. Mutant 274(Asn-->Thr), showed slight reduction. Neither mutant recorded ML-17-equivalent attenuation, implying that prM/M changes need to combine with other recorded genomic differences to cause attenuation. Importantly, ML-17 with its unchanged E region, presents a possible backbone candidate for preparation of "E-replacement" type live attenuated flavivirus chimeric vaccines.
Shah
Paresh Sumatilal
PS
Department of Virology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Tanaka
Mariko
M
Khan
Afjal Hossain
AH
Mathenge
Edward Gitau Matumbi
EG
Fuke
Isao
I
Takagi
Mitsuo
M
Igarashi
Akira
A
Morita
Kouichi
K
D000818:Animals; D004664:Encephalitis Virus, Japanese / Q000235:genetics* / Q000472:pathogenicity; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D017421:Sequence Analysis; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D014774:Virulence / Q000235:genetics
D022321:Japanese Encephalitis Vaccines; D014613:Vaccines, Attenuated