title: Effects of route and coadministration of recombinant raccoon poxviruses on immune responses and protection against highly pathogenic avian influenza in mice.
abstract: We previously demonstrated that recombinant raccoonpox (RCN) virus could serve as a vector for an influenza vaccine. RCN constructs expressing the hemagglutinin (HA) from H5N1 viruses were immunogenic in chickens. In the current study, we generated several recombinant RCN constructs expressing influenza (H5N1) antigens and a molecular adjuvant (Heat-Labile enterotoxin B from E. coli: RCN-LTB), demonstrated their expression in vitro, and evaluated their ability to protect mice against H5N1 virus challenge. RCN-HA provided strong protection when administered intradermally (ID), but not intranasally (IN). Conversely, the RCN-neuraminidase (NA) construct was highly efficacious by the IN route and elicited high titers of neutralizing antibodies in mice. Vaccination by combined ID (RCN-HA) and IN (RCN-NA) routes offered mice the best protection against an IN challenge with heterologous H5N1 virus. However, protection was reduced when the different RCN constructs were pre-mixed, perhaps due to reduced expression of antigen.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Brock
authors.initials: B
authors.lastname: Kingstad-Bakke
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Brewoo
authors.forename: Le Quynh
authors.initials: le Q
authors.lastname: Mai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Osorio
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D007271:Injections, Intradermal; D051379:Mice; D008805:Mice, Inbred A; D009439:Neuraminidase / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011212:Poxviridae / Q000276:immunology*; D014611:Vaccination / Q000379:methods
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D009439:Neuraminidase