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Published online ahead of print on 4 March 2009 as doi:10.1099/vir.0.006833-0
Journal of General Virology 2009;90:874.

A more recent version of this article appeared on April 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.006833-0
© 2009 Society for General Microbiology

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Interferon alpha as an adenovirus-vectored vaccine adjuvant and antiviral in Venezuelan equine encephalitis virus infection

Lyn O'Brien1,3, Stuart Perkins1, Amanda Williams1, Lin Eastaugh1, Amanda Phelps1, Josh Wu2 and Robert Phillpotts1

1 Dstl;
2 DRDC

3 E-mail: lmobrien{at}dstl.gov.uk

There are no widely available vaccines or antiviral drugs capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), although an adenovirus vector expressing VEEV structural proteins protects mice from challenge with VEEV and is potentially a vaccine suitable for human use. This work examines whether interferon alpha (IFN-{alpha}) could act as an adjuvant for the adenovirus-based vaccine. IFN-{alpha} was expressed either by a plasmid linked to the adenovirus vaccine or was encoded by a separate adenovirus vector administered as a mixture with the vaccine. In contrast to previous reports with other vaccines, the presence of IFN-{alpha} decreased the antibody response to VEEV. When IFN-{alpha} was encoded by adenovirus, the lack of a VEEV-specific response was accompanied by an increase in the immune response to the adenovirus vector. IFN-{alpha} also plays a direct role in defence against viral infection, inducing the expression of a large number of antiviral proteins. Adenovirus-delivered IFN-{alpha} protected mice from VEEV disease when administered 24 h prior to challenge but not 6 h post-challenge, suggesting that up to 24 h was required for the development of the interferon-mediated antiviral response.© Crown Copyright. Dstl, 2008

Received 26 August 2008; accepted 7 December 2008.





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