TY - JOUR
T1 - Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain
AU - Mellado-Sanchez, Gabriela
AU - Ramirez, Karina
AU - Drachenberg, Cinthia B.
AU - Diaz-McNair, Jovita
AU - Rodriguez, Ana L.
AU - Galen, James E.
AU - Nataro, James P.
AU - Pasetti, Marcela F.
N1 - Funding Information:
The authors acknowledge Dr. Scott A. Lloyd for the construction of plasmids, expertise and critical discussions and Mr. Cesar Paz, Ms. Kitty Davis and personnel from the Applied Immunology Section for exceptional technical assistance. G.M. received a post-doctoral fellowship (2008–2009) from the National Council of Science and Technology, México . This work was supported, in part, by National Institute of Health grants U19-AI-56578 (to J.P.N.), U01-AI077911 (to J.P.N and J.E.G) and R01-AI065760 (to M.F.P.).
PY - 2013/3
Y1 - 2013/3
N2 - Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered as a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings.
AB - Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered as a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings.
KW - EV76
KW - Plague infection model
KW - Plague vaccines
KW - Yersinia pestis
UR - http://www.scopus.com/inward/record.url?scp=84875247015&partnerID=8YFLogxK
U2 - 10.1016/j.cimid.2012.10.005
DO - 10.1016/j.cimid.2012.10.005
M3 - Artículo
SN - 0147-9571
VL - 36
SP - 113
EP - 128
JO - Comparative Immunology, Microbiology and Infectious Diseases
JF - Comparative Immunology, Microbiology and Infectious Diseases
IS - 2
ER -