Abstract

Yersinia pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. There are several thousand reported cases of the disease worldwide annually and an emergence of Y. pestis strains resistant to multiple drugs. Plague has been classified as a re-emerging disease by the World Health Organization and Y. pestis is considered a potential bioweapon owing to its extreme virulence. Despite a need, there are no licensed plague vaccines available in the United States currently. Because of these considerations, we will construct highly attenuated Y. pestis and Y. pseudotuberculosis strains modified to express selected Y. pestis protective antigens at higher than normal levels for use as vaccines. Our studies will focus on evaluating the efficacy of these strains against a high-dose pneumonic and subcutaneous Y. pestis challenge. Attenuated Y. pseudotuberculosis vaccine strains vectoring Y. pestis antigens (LcrV and/or F1) and selected Y. pestis vaccine strains will be evaluated as oral vaccines against high-dose Y. pestis challenges by both pneumonic and bubonic routes of infection.

Public Health Relevance

Y. pestis, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. There are no licensed plague vaccines available in the United States currently. We will explore using live attenuated Yersinia synthesizing high levels of selected Y. pestis antigens as a vaccine against bubonic and pneumonic plague. These studies will provide us with live attenuated Yersinia vaccine candidates suitable for use in humans and as a zoonotic vaccine suitable for use in rodent baits.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI095872-02
Application #
8339445
Study Section
Vaccines Against Microbial Diseases (VMD)
Program Officer
Zou, Lanling
Project Start
2011-09-30
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$228,750
Indirect Cost
$78,750

  Institution

Name
Arizona State University-Tempe Campus
Department
Other Health Professions
Type
Organized Research Units
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287