Semliki Forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems.
This study has examined the persistence, distribution and pathological changes following intramuscular administration of Semliki Forest virus (SFV) vaccine vectors in mice and chickens. Administration of recombinant SFV RNA particles showed persistence at the injection site of mice up to 7 days, transient detection in secondary lymphoid organs and no dissemination to distal sites. In contrast, administration of a layered SFV DNA/RNA vector and a conventional standard naked DNA vector resulted in long-term persistence at the injection site, plasmid DNA being detected at 8 months post-inoculation in mice. Plasmid DNA was found distributed throughout the body, and tissues distal from the site of injection were positive up to 3 months. A similar pattern was observed in chickens. Mild pathological changes were observed at the injection site only, and plasmid DNA or recombinant RNA was not detected in mouse foetuses. These findings indicate that SFV-based vectors have the potential to be developed as safe vaccines.
Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, 2, Dublin, Ireland.
M M
MM
Morris-Downes
K V
KV
Phenix
J
J
Smyth
B J
BJ
Sheahan
S
S
Lileqvist
D A
DA
Mooney
P
P
Liljeström
D
D
Todd
G J
GJ
Atkins
D000818:Animals; D001483:Base Sequence; D002645:Chickens; D017931:DNA Primers / Q000235:genetics; D005260:Female; D049452:Green Fluorescent Proteins; D007273:Injections, Intramuscular; D008164:Luminescent Proteins / Q000235:genetics; D008431:Maternal-Fetal Exchange; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000473:pathology; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D012449:Safety; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology*; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D019444:Vaccines, DNA / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D014614:Vaccines, Synthetic / Q000235:genetics / Q000494:pharmacology / Q000633:toxicity; D014765:Viral Vaccines / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity
D017931:DNA Primers; D008164:Luminescent Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D049452:Green Fluorescent Proteins