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

Vaccine. 2008 May 23;26(22):2772-81. doi: 10.1016/j.vaccine.2008.03.010. Epub 2008 Mar 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Cricetinae
  • Encephalitis, Japanese / prevention & control*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Japanese Encephalitis Vaccines / genetics*
  • Japanese Encephalitis Vaccines / immunology*
  • Mice
  • Neutralization Tests
  • Survival Analysis
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • West Nile Fever / prevention & control
  • West Nile virus / genetics
  • West Nile virus / growth & development

Substances

  • Antibodies, Viral
  • Japanese Encephalitis Vaccines
  • Vaccines, Synthetic
  • Viral Proteins