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.