title: Protective immunity against respiratory tract challenge with Yersinia pestis in mice immunized with an adenovirus-based vaccine vector expressing V antigen.
abstract: The aerosol form of the bacterium Yersinia pestis causes the pneumonic plague, a rapidly fatal disease. At present, no plague vaccines are available for use in the United States. One candidate for the development of a subunit vaccine is the Y. pestis virulence (V) antigen, a protein that mediates the function of the Yersinia outer protein virulence factors and suppresses inflammatory responses in the host. On the basis of the knowledge that adenovirus (Ad) gene-transfer vectors act as adjuvants in eliciting host immunity against the transgene they carry, we tested the hypothesis that a single administration of a replication-defective Ad gene-transfer vector encoding the Y. pestis V antigen (AdsecV) could stimulate strong protective immune responses without a requirement for repeat administration. AdsecV elicited specific T cell responses and high IgG titers in serum within 2 weeks after a single intramuscular immunization. Importantly, the mice were protected from a lethal intranasal challenge of Y. pestis CO92 from 4 weeks up to 6 months after immunization with a single intramuscular dose of AdsecV. These observations suggest that an Ad gene-transfer vector expressing V antigen is a candidate for development of an effective anti-plague vaccine.
authors.affiliation: Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Chiuchiolo
authors.forename: Julie L
authors.initials: JL
authors.lastname: Boyer
authors.forename: Anja
authors.initials: A
authors.lastname: Krause
authors.forename: Svetlana
authors.initials: S
authors.lastname: Senina
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010930:Plague / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology* / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D014614:Vaccines, Synthetic