Semliki Forest virus-based vaccines: persistence, distribution and pathological analysis in two animal systems

This study has examined the persistence, distribution and pathological chan ges following intramuscular administration of Semliki Forest virus (SFV) va ccine vectors in mice and chickens. Administration of recombinant SFV RNA p articles showed persistence at the injection site of mice up to 7 days, tra nsient detection in secondary lymphoid organs and no dissemination to dista l 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-inoculatio n in mice. Plasmid DNA was found distributed throughout the body, and tissu es distal from the site of injection were positive up to 3 months. A simila r pattern was observed in chickens. Mild pathological changes were observed at the injection site only, and plasmid DNA or recombinant RNA was not det ected in mouse foetuses. These findings indicate that SFV-based vectors hav e the potential to be developed as safe vaccines. (C) 2001 Elsevier Science Ltd. All rights reserved.