title: Development of a vaccinia virus based reservoir-targeted vaccine against Yersinia pestis.
abstract: Yersinia pestis, the causative organism of plague, is a zoonotic organism with a worldwide distribution. Although the last plague epidemic occurred in early 1900s, human cases continue to occur due to contact with infected wild animals. In this study, we have developed a reservoir-targeted vaccine against Y. pestis, to interrupt transmission of disease in wild animals as a potential strategy for decreasing human disease. A vaccinia virus delivery system was used to express the F1 capsular protein and the LcrV type III secretion component of Y. pestis as a fusion protein. Here we show that a single dose of this vaccine administered orally, generates a dose-dependent antibody response in mice. Antibody titers peak by 3 weeks after administration and remain elevated for a minimum of 45 weeks. Vaccination provided up to 100% protection against challenge with Y. pestis administered by intranasal challenge at 10 times the lethal dose with protection lasting a minimum of 45 weeks. An orally available, vaccinia virus expressed vaccine against Y. pestis may be a suitable vaccine for a reservoir targeted strategy for the prevention of enzootic plague.
authors.affiliation: Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA.
authors.forename: Debaditya
authors.initials: D
authors.lastname: Bhattacharya
authors.forename: Joan
authors.initials: J
authors.lastname: Mecsas
authors.forename: Linden T
authors.initials: LT
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D004197:Disease Reservoirs / Q000382:microbiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010930:Plague / Q000276:immunology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C086725:caf1 protein, Yersinia pestis