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JSPS RONPAKU (DISSERTATION PhD) PROGRAM

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Dissertation Abstracts

India
Name Paresh Sumatilal SHAH
Position Research Officer
National Institute of Virology
Japanese Advisor Koichi MORITA
Professor,Nagasaki University

Molecular characterization of attenuated Japanese encephalitis live vaccine strain ML-17

  The ML-17 strain is the only officially approved commercial live attenuated-JE vaccine for animals in Japan. In order to provide more chimeric scaffolds the study was undertaken to establish the attenuation characteristics of the ML17.
  The 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 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, two mutants bearing the changes were prepared (MS-14 and MS-15) using another virulent strain isolated from Osaka namely JaOArS982. Both mutants demonstrated slight reduction of plaque size and reduction of neurovirulence in mice compared to parent strain JaOArS982 used to generate mutants. 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.

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