DNA-BASED AND ALPHAVIRUS-VECTORED IMMUNIZATION WITH PRM AND E-PROTEINS ELICITS LONG-LIVED AND PROTECTIVE IMMUNITY AGAINST THE FLAVIVIRUS, MURRAY-VALLEY-ENCEPHALITIS-VIRUS

The immunogenicity and protective efficacy of DNA-based vaccination wi th plasmids encoding the membrane proteins prM and E of the flavivirus Murray Valley encephalitis virus (MVE) were investigated. Gene gun-me diated intradermal delivery of DNA encoding the prM and E proteins eli cited long-lived, virus-neutralising antibody responses in three inbre d strains of mice and provided protection from challenge with a high t iter inoculum of MVE. Intramuscular DNA vaccination by needle injectio n also induced MVE-specific antibodies that conferred resistance to ch allenge with live Virus but failed to reduce virus infectivity in vitr o. The two routes of DNA-based vaccination with prM and E encoding pla smids resulted in humoral immunty with distinct IgG subtypes. MVE-spec ific IgG(1) antibodies were always prevalent after intradermal DNA Vac cination via a gene gun but not detected when mice were immunised with DNA by the intramuscular route or infected with live virus. We also t ested a Semliki Forest virus replicon as vector for a flavivirus prM a nd E protein-based subunit vaccine. Single-cycle infections in mice va ccinated with packaged recombinant replicon particles elicited durable , MvE-specific, and virus-neutralising antibody responses. (C) 1998 Ac ademic Press.