title: Plague in Guinea pigs and its prevention by subunit vaccines.
abstract: Human pneumonic plague is a devastating and transmissible disease for which a Food and Drug Administration-approved vaccine is not available. Suitable animal models may be adopted as a surrogate for human plague to fulfill regulatory requirements for vaccine efficacy testing. To develop an alternative to pneumonic plague in nonhuman primates, we explored guinea pigs as a model system. On intranasal instillation of a fully virulent strain, Yersinia pestis CO92, guinea pigs developed lethal lung infections with hemorrhagic necrosis, massive bacterial replication in the respiratory system, and blood-borne dissemination to other organ systems. Expression of the Y. pestis F1 capsule was not required for the development of pulmonary infection; however, the capsule seemed to be important for the establishment of bubonic plague. The mean lethal dose (MLD) for pneumonic plague in guinea pigs was estimated to be 1000 colony-forming units. Immunization of guinea pigs with the recombinant forms of LcrV, a protein that resides at the tip of Yersinia type III secretion needles, or F1 capsule generated robust humoral immune responses. Whereas LcrV immunization resulted in partial protection against pneumonic plague challenge with 250 MLD Y. pestis CO92, immunization with recombinant F1 did not. rV10, a vaccine variant lacking LcrV residues 271-300, elicited protection against pneumonic plague, which seemed to be based on conformational antibodies directed against LcrV.
authors.affiliation: Department of Microbiology, The University of Chicago, Chicago, Illinois; Howard Taylor Ricketts Laboratory, Argonne National Laboratory, Argonne, IL 60637, USA.
authors.forename: Lauriane E
authors.initials: LE
authors.lastname: Quenee
authors.forename: Nancy
authors.initials: N
authors.lastname: Ciletti
authors.forename: Bryan
authors.initials: B
authors.lastname: Berube
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausz
authors.forename: Derek
authors.initials: D
authors.lastname: Elli
authors.forename: Timothy
authors.initials: T
authors.lastname: Hermanas
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007107:Immune System; D008168:Lung / Q000382:microbiology; D010930:Plague / Q000503:physiopathology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000627:therapeutic use; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D013154:Spleen / Q000382:microbiology; D022223:Vaccines, Subunit / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000737:chemistry; D015010:Yersinia pestis / Q000378:metabolism
chemical_list: D010931:Plague Vaccine; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic