title: Yersinia pestis caf1 variants and the limits of plague vaccine protection.
abstract: Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Lauriane E
authors.initials: LE
authors.lastname: Quenee
authors.forename: Claire A
authors.initials: CA
authors.lastname: Cornelius
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Ciletti
authors.forename: Derek
authors.initials: D
authors.lastname: Elli
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015169:Colony Count, Microbial; D005260:Female; D017353:Gene Deletion; D007074:Immunoglobulin G / Q000097:blood; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence; D015010:Yersinia pestis / Q000235:genetics* / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D014613:Vaccines, Attenuated; C086725:caf1 protein, Yersinia pestis