title: Protection against pneumonic plague following oral immunization with a non-replicating vaccine.
abstract: Yersinia pestis is a dangerous bacterial pathogen that when inhaled can rapidly induce fatal pneumonic plague. Thus, there is a need for stable, safe, and easily administered mucosal vaccines capable of eliciting effective protection against pulmonary Y. pestis infections. Cationic liposome-nucleic acid complexes (CLDC) have been shown previously to be effective vaccine adjuvants for parenteral immunization, but have not been previously evaluated for use in oral immunization. Therefore, we investigated the ability of an orally administered CLDC adjuvanted vaccine to elicit protective immunity against lethal pneumonic plague. C57Bl/6 mice were vaccinated orally or subcutaneously using 10mug Y. pestis F1 antigen combined with CLDC and immune responses and protection from challenge was assessed. We found that oral immunization elicited high titers of anti-F1 antibodies, equivalent to those generated by parenteral immunization. Importantly, orally immunized mice were protected from lethal pulmonary challenge with virulent Y. pestis for up to 18 weeks following vaccination. Vaccine-induced protection following oral immunization was found to be dependent primarily on CD4+ T cells, with a partial contribution from CD8+ T cells. Thus, CLDC adjuvanted vaccines represent a new type of orally administered, non-replicating vaccine capable of generating effective protection against pulmonary infection with virulent Y. pestis.
authors.affiliation: Dept of Microbiology, Immunology, and Pathology, Colorado State University, Ft. Collins, CO 80523, USA.
authors.forename: Abby
authors.initials: A
authors.lastname: Jones
authors.forename: Catharine
authors.initials: C
authors.lastname: Bosio
authors.forename: Angela
authors.initials: A
authors.lastname: Duffy
authors.forename: Andrew
authors.initials: A
authors.lastname: Goodyear
authors.forename: Martin
authors.initials: M
authors.lastname: Schriefer
authors.forename: Steven
authors.initials: S
authors.lastname: Dow
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D056724:Immunity, Humoral; D008081:Liposomes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010930:Plague / Q000276:immunology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D008081:Liposomes; D010931:Plague Vaccine; C086725:caf1 protein, Yersinia pestis