title: Single-shot immunization with recombinant adenovirus encoding vaccinia virus glycoprotein A27L is protective against a virulent respiratory poxvirus infection.
abstract: Significant safety issues have emerged concerning the general use of DRYVAX vaccine. Vaccination with replication-defective recombinant adenovirus (rAd) vaccines may offer a safer and effective alternative to live vaccinia virus (VV) vaccination. Six individual poxvirus glycoproteins: A33R, A34R, A36R, B5R, A27L or L1R that are normally expressed on the surface of infectious vaccinia virus were encoded in rAd vaccines and tested in mice in this study. A single-shot intramuscular injection of rAd encoding A27L protected mice against a lethal intranasal challenge with VV at 4 weeks post-vaccination. By 10 weeks post-vaccination, a significant decrease in post-challenge morbidity was observed that correlated with potent neutralizing antibody responses and the emergence of specific polyfunctional T cell responses. The immunogenicity and protective efficacy of rAd-A27L immunization persisted for at least 35 weeks post-vaccination. This study is the first demonstration that a single-shot subunit vaccine encoding a poxvirus protein confers protection against the mortality and morbidity associated with poxvirus infection.
authors.affiliation: Gene Therapy Program, and Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Rudraraju
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Ramsay
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D012899:Smallpox / Q000276:immunology / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
chemical_list: C110360:A27L protein, Orthopoxvirus; D000914:Antibodies, Viral; D012900:Smallpox Vaccine; D014614:Vaccines, Synthetic; D014764:Viral Proteins