title: Complete protection of mice against a lethal dose challenge of western equine encephalitis virus after immunization with an adenovirus-vectored vaccine.
abstract: Western equine encephalitis virus (WEEV) is an important pathogen for both humans and equines. The virus is also listed as a bioterrorism agent due to its ability for aerosol transmission with high mortality. No commercial vaccines or antiviral drugs are available for the prevention and treatment of WEEV infection in humans. In this paper, we constructed a recombinant WEEV vaccine, designated as Ad5-WEEV, using a replication defective, human adenovirus serotype 5 (HAd5) as a delivery vector. Ad5-WEEV contains the E3-E2-6K-E1 structural protein gene of the 71V-1658 strain of WEEV and the E1 and E2 proteins were synthesized in cells inoculated with Ad5-WEEV. After intramuscular immunization of mice with two doses of Ad5-WEEV, neutralizing antibodies against WEEV were generated and the mice were completely protected from a lethal dose challenge of 71V-1658. In addition, we showed that passive transfer of serum from the Ad5-WEEV-immunized mice could partially control WEEV infection. These results demonstrate that HAd5 vectors are promising for WEEV vaccine development.
authors.affiliation: Chemical and Biological Defence Section, Defence Research and Development Canada-Suffield, Box 4000, Station Main, Medicine Hat, Alberta, Canada. josh.wu@drdc-rddc.gc.ca
authors.forename: Josh Q H
authors.initials: JQ
authors.lastname: Wu
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Barabé
authors.forename: Damon
authors.initials: D
authors.lastname: Chau
authors.forename: Christina
authors.initials: C
authors.lastname: Wong
authors.forename: George R
authors.initials: GR
authors.lastname: Rayner
authors.forename: Wei-Gang
authors.initials: WG
authors.lastname: Hu
authors.forename: Les P
authors.initials: LP
authors.lastname: Nagata
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D002522:Chlorocebus aethiops; D015195:Drug Design; D004667:Encephalitis Virus, Western Equine / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D020241:Encephalomyelitis, Western Equine / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D051379:Mice; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014709:Vero Cells; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D014614:Vaccines, Synthetic; D015678:Viral Structural Proteins; D014765:Viral Vaccines