title: Protective immunity against a lethal respiratory Yersinia pestis challenge induced by V antigen or the F1 capsular antigen incorporated into adenovirus capsid.
abstract: The aerosol form of the bacterium Yersinia pestis causes pneumonic plague, a rapidly fatal disease that is a biothreat if deliberately released. At present, no plague vaccines are available for use in the United States, but subunit vaccines based on the Y. pestis V antigen and F1 capsular protein show promise when administered with adjuvants. In the context that adenovirus (Ad) gene transfer vectors have a strong adjuvant potential related to the ability to directly infect dendritic cells, we hypothesized that modification of the Ad5 capsid to display either the Y. pestis V antigen or the F1 capsular antigen on the virion surface would elicit high V antigen- or F1-specific antibody titers, permit boosting with the same Ad serotype, and provide better protection against a lethal Y. pestis challenge than immunization with equivalent amounts of V or F1 recombinant protein plus conventional adjuvant. We constructed AdYFP-pIX/V and AdLacZ-pIX/F1, E1(-), E3(-) serotype 5 Ad gene transfer vectors containing a fusion of the sequence for either the Y. pestis V antigen or the F1 capsular antigen to the carboxy-terminal sequence of pIX, a capsid protein that can accommodate the entire V antigen (37 kDa) or F1 protein (15 kDa) without disturbing Ad function. Immunization with AdYFP-pIX/V followed by a single repeat administration of the same vector at the same dose resulted in significantly better protection of immunized animals compared with immunization with a molar equivalent amount of purified recombinant V antigen plus Alhydrogel adjuvant. Similarly, immunization with AdLacZ-pIX/F1 in a prime-boost regimen resulted in significantly enhanced protection of immunized animals compared with immunization with a molar-equivalent amount of purified recombinant F1 protein plus adjuvant. These observations demonstrate that Ad vaccine vectors containing pathogen-specific antigens fused to the pIX capsid protein have strong adjuvant properties and stimulate more robust protective immune responses than equivalent recombinant protein-based subunit vaccines administered with conventional adjuvant, suggesting that F1-and/or V-modified capsid Ad-based recombinant vaccines should be considered for development as anti-plague vaccines.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College , New York, NY 10026, USA.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Boyer
authors.forename: Carolina
authors.initials: C
authors.lastname: Sofer-Podesta
authors.forename: John
authors.initials: J
authors.lastname: Ang
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Chiuchiolo
authors.forename: Svetlana
authors.initials: S
authors.lastname: Senina
authors.forename: David
authors.initials: D
authors.lastname: Perlin
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D015153:Blotting, Western; D002213:Capsid; D005822:Genetic Vectors; D007114:Immunization; D010930:Plague / Q000276:immunology / Q000517:prevention & control; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C043908:LcrV protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; C086725:caf1 protein, Yersinia pestis