Molecular Characterization of Attenuated Japanese Encephalitis Live Vaccine Strain Ml-17.
From: Department of Virology, Institute of Tropical Medicine, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Vaccine
- Publish Date: Jan 2006
- ISSN: 0264-410X
- Volume: 24
- Issue: 4
- Pages: 402-11
- Medium: Print
- Language: English
- Citation (JAMA): Shah Paresh Sumatilal, Tanaka Mariko, Khan Afjal Hossain, et al. Molecular Characterization of Attenuated Japanese Encephalitis Live Vaccine Strain Ml-17.. Vaccine Jan 2006;24:402-11
Abstract
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.
Mesh Headings (Keywords): Animals, Encephalitis Virus, Japanese, Encephalitis, Japanese, Japanese Encephalitis Vaccines, Mice, Molecular Sequence Data, Sequence Analysis, Vaccines, Attenuated, Virulence
Check for Full Text / PubMed Unique Identifier (PMID): 16303214
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