DNA-based and alphavirus-vectored immunisation with prM and E proteins elicits long-lived and protective immunity against the flavivirus, Murray Valley encephalitis virus

Abstract

The immunogenicity and protective efficacy of DNA-based vaccination with plasmids encoding the membrane proteins prM and E of the flavivirus Murray Valley encephalitis virus (MVE) were investigated. Gene gun-mediated intradermal delivery of DNA encoding the prM and E proteins elicited long-lived, virus-neutralising antibody responses in three inbred strains of mice and provided protection from challenge with a high titer inoculum of MVE. Intramuscular DNA vaccination by needle injection also induced MVE-specific antibodies that conferred resistance to challenge with live virus but failed to reduce virus infectivity in vitro. The two routes of DNA-based vaccination with prM and E encoding plasmids resulted in humoral immunty with distinct IgG subtypes. MVE-specific IgG1 antibodies were always prevalent after intradermal DNA vaccination via a gene gun but not detected when mice were immunised with DNA by the intramuscular route or infected with live virus. We also tested a Semliki Forest virus replicon as vector for a flavivirus prM and E protein-based subunit vaccine. Single-cycle infections in mice vaccinated with packaged recombinant replicon particles elicited durable, MVE-specific, and virus-neutralising antibody responses.