In this renewal application we propose to continue our multidisciplinary approach to the study of Bacillus anthracis infections in humans. We view B. anthracis as one of the most significant threats to our society as a bioterrorist agent, distinct from its use as a biological weapon. B. anthracis is alarming as a weapon of terror for several reasons: 1) the spore is long-lived and stable in harsh environments;2) the vaccine is poor, of questionable efficacy, has a cumbersome injection schedule, and is not provided to civilians;3) there are no effective treatments for the disease;4) a small number of deaths from a rare and thus exotic disease is sufficient to cause terror in our population. Indeed, this is exactly what happened after the US Postal Service Center attacks in 2001. Our application builds on a previously funded U19 to study the human and non-human primate response to B. anthracis infections and immunizations. During the first grant period, we built an organization with remarkable physical and intellectual assets and a superb infrastructure. The group we assembled is productive, highly interactive and has a formidable background in immunology. Our group includes faculty, fellows, technicians, veterinary staff and other support staff at four different institutions: The Oklahoma Medical Research Foundation, The University of Oklahoma, and now The University of Chicago, and Boston University. The application contains five Scientific Projects, three Technical Projects and two Core Facilities (along with Administrative and Educational cores). We attack the problem from every direction: powerful experimental models largely developed in house, a novel approach to vaccine genetics and vaccine efficacy, several host-response issues, studies of the exotoxins, and two novel and exciting therapeutic approaches. Overall, we are confident that the four years of funding puts us in a competitive position to exploit the findings of our first cycle to make substantive advances in the next five years.

Public Health Relevance

B. anthracis is highly relevant and important agent of bioterrorism. Although a vaccine is provided to military personnel, it is not given to private citizens and is of highly questionable efficacy. There is very little understood of B. anthracis infections in humans, largely because anthrax is only a weapon of terror and natural human infections occur rarely.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI062629-10
Application #
8526353
Study Section
Special Emphasis Panel (ZAI1-KS-I (J3))
Program Officer
Breen, Joseph J
Project Start
2004-09-15
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
10
Fiscal Year
2013
Total Cost
$2,703,462
Indirect Cost
$661,322
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
077333797
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
More, Sunil; Yang, Xiaoyun; Zhu, Zhengyu et al. (2018) Regulation of influenza virus replication by Wnt/?-catenin signaling. PLoS One 13:e0191010
Hu, Zihua; Jiang, Kaiyu; Frank, Mark Barton et al. (2018) Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis. Sci Rep 8:7805
Booth, J Leland; Duggan, Elizabeth S; Patel, Vineet I et al. (2018) Gene expression profiling of primary human type I alveolar epithelial cells exposed to Bacillus anthracis spores reveals induction of neutrophil and monocyte chemokines. Microb Pathog 121:9-21
Seshadri, Sudarshan; Pope, Rosemary L; Zenewicz, Lauren A (2018) Glucocorticoids Inhibit Group 3 Innate Lymphocyte IL-22 Production. J Immunol 201:1267-1274
Girton, Alanson W; Popescu, Narcis I; Keshari, Ravi S et al. (2018) Serum Amyloid P and IgG Exhibit Differential Capabilities in the Activation of the Innate Immune System in Response to Bacillus anthracis Peptidoglycan. Infect Immun 86:
Langer, Marybeth; Girton, Alanson W; Popescu, Narcis I et al. (2018) Neither Lys- and DAP-type peptidoglycans stimulate mouse or human innate immune cells via Toll-like receptor 2. PLoS One 13:e0193207
DeVette, Christa I; Andreatta, Massimo; Bardet, Wilfried et al. (2018) NetH2pan: A Computational Tool to Guide MHC Peptide Prediction on Murine Tumors. Cancer Immunol Res 6:636-644
Popescu, Narcis I; Silasi, Robert; Keshari, Ravi S et al. (2018) Peptidoglycan induces disseminated intravascular coagulation in baboons through activation of both coagulation pathways. Blood 132:849-860
Fuentes-Mattei, Enrique; Giza, Dana Elena; Shimizu, Masayoshi et al. (2017) Plasma Viral miRNAs Indicate a High Prevalence of Occult Viral Infections. EBioMedicine 20:182-192
Dumas, Eric K; Garman, Lori; Cuthbertson, Hannah et al. (2017) Lethal factor antibodies contribute to lethal toxin neutralization in recipients of anthrax vaccine precipitated. Vaccine 35:3416-3422

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