Alpha interferon as an adenovirus-vectored vaccine adjuvant and antiviral in Venezuelan equine encephalitis virus infection.
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.
O'Brien
Lyn
L
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Perkins
Stuart
S
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Williams
Amanda
A
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Eastaugh
Lin
L
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Phelps
Amanda
A
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Wu
Josh
J
Biotechnology Section, Defence Research and Development Canada - Suffield, Box 4000, Station Main, Medicine Hat, Alberta T1A 8K6, Canada.
Phillpotts
Robert
R
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
D000260:Adenoviruses, Human / Q000235:genetics*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology; D001921:Brain / Q000821:virology; D002460:Cell Line; D002522:Chlorocebus aethiops; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology / Q000472:pathogenicity; D004685:Encephalomyelitis, Venezuelan Equine / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D007739:L Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors; D016896:Treatment Outcome; D014709:Vero Cells; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000998:Antiviral Agents; D007074:Immunoglobulin G; D016898:Interferon-alpha; D014765:Viral Vaccines