Construction and evaluation of a chimeric pseudoinfectious virus vaccine to prevent Japanese encephalitis

Tomohiro Ishikawa, Douglas G. Widman, Nigel Bourne, Eiji Konishi, Peter W. Mason

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Multiple vaccines exist to control Japanese encephalitis (JE), but all suffer from problems. We have developed a new type of flavivirus vaccine, a pseudoinfectious virus (RepliVAX WN) that prevents West Nile virus (WNV)-induced disease. Here, we describe production of a chimeric RepliVAX (RepliVAX JE) that expresses the JE virus (JEV) prM and E proteins. Our prototype RepliVAX JE replicated poorly in cells, but blind passage produced a better-growing derivative, and analyses of this derivative allowed us to engineer a second-generation RepliVAX (RepliVAX JE.2) that grew to high titers. RepliVAX JE.2 elicited neutralizing antibodies in both mice and hamsters and provided 100% protection from a lethal challenge with JEV or WNV, respectively. These results demonstrate the utility our RepliVAX platform for producing a JE vaccine.

Original languageEnglish (US)
Pages (from-to)2772-2781
Number of pages10
JournalVaccine
Volume26
Issue number22
DOIs
StatePublished - May 23 2008

Keywords

  • Chimera
  • Encephalitis virus
  • Japanese
  • Subviral particle

ASJC Scopus subject areas

  • Molecular Medicine
  • General Immunology and Microbiology
  • General Veterinary
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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