J Gen Virol
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Originally published as JGV in Press, 10.1099/vir.0.006833-0 on March 4, 2009 J Gen Virol 90 (2009), 874-882; DOI 10.1099/vir.0.006833-0

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Alpha interferon as an adenovirus-vectored vaccine adjuvant and antiviral in Venezuelan equine encephalitis virus infection

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

1 Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK
2 Biotechnology Section, Defence Research and Development Canada – Suffield, Box 4000, Station Main, Medicine Hat, Alberta T1A 8K6, Canada

Correspondence
Lyn O'Brien
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 alpha interferon (IFN-{alpha}) could act as an adjuvant for the adenovirus-based vaccine. IFN-{alpha} was either expressed by a plasmid linked to the adenovirus vaccine or 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} reduced 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 virus 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 when administered 6 h post-challenge, suggesting that up to 24 h is required for the development of the IFN-mediated antiviral response.






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