DNA-based and alphavirus-vectored immunisation 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 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.
John Curtin School of Medical Research, The Australian National University, Canberra, ACT, 2601, Australia.
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Colombage
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Hall
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Pavy
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Lobigs
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D019470:Biolistics; D019556:COS Cells; D018068:Encephalitis Virus, Murray Valley / Q000276:immunology*; D004671:Encephalitis, Arbovirus / Q000517:prevention & control*; D005822:Genetic Vectors / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008815:Mice, Inbred Strains; D009500:Neutralization Tests; D010957:Plasmids / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins; D012672:Semliki forest virus / Q000235:genetics; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C074932:prM protein, Flavivirus; C065696:glycoprotein E, Flavivirus