title: An adenovirus-based vaccine with a double-stranded RNA adjuvant protects mice and ferrets against H5N1 avian influenza in oral delivery models.
abstract: An oral gene-based avian influenza vaccine would allow rapid development and simplified distribution, but efficacy has previously been difficult to achieve by the oral route. This study assessed protection against avian influenza virus challenge using a chimeric adenovirus vector expressing hemagglutinin and a double-stranded RNA adjuvant. Immunized ferrets and mice were protected upon lethal challenge. Further, ferrets immunized by the peroral route induced cross-clade neutralizing antibodies, and the antibodies were selective against hemagglutinin, not the vector. Similarly, experiments in mice demonstrated selective immune responses against HA with peroral delivery and the ability to circumvent preexisting vector immunity.
authors.affiliation: Vaxart, Inc., San Francisco, CA, USA.
authors.forename: Ciaran D
authors.initials: CD
authors.lastname: Scallan
authors.forename: Debora W
authors.initials: DW
authors.lastname: Tingley
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Lindbloom
authors.forename: James S
authors.initials: JS
authors.lastname: Toomey
authors.forename: Sean N
authors.initials: SN
authors.lastname: Tucker
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D004195:Disease Models, Animal; D004337:Drug Carriers; D005289:Ferrets; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D012330:RNA, Double-Stranded / Q000008:administration & dosage* / Q000235:genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004337:Drug Carriers; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D012330:RNA, Double-Stranded; D014614:Vaccines, Synthetic; C109963:hemagglutinin, avian influenza A virus