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 #
5U19AI062629-08
Application #
8137861
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
2011-09-01
Budget End
2012-08-31
Support Year
8
Fiscal Year
2011
Total Cost
$2,840,289
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
077333797
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
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
Keshari, Ravi S; Silasi, Robert; Lupu, Cristina et al. (2017) In vivo-generated thrombin and plasmin do not activate the complement system in baboons. Blood 130:2678-2681
Marsman, Gerben; von Richthofen, Helen; Bulder, Ingrid et al. (2017) DNA and factor VII-activating protease protect against the cytotoxicity of histones. Blood Adv 1:2491-2502
Remesh, Soumya G; Andreatta, Massimo; Ying, Ge et al. (2017) Unconventional Peptide Presentation by Major Histocompatibility Complex (MHC) Class I Allele HLA-A*02:01: BREAKING CONFINEMENT. J Biol Chem 292:5262-5270
Healy, Laura D; Puy, Cristina; Fernández, José A et al. (2017) Activated protein C inhibits neutrophil extracellular trap formation in vitro and activation in vivo. J Biol Chem 292:8616-8629
Dumas, Eric K; Gross, Timothy; Larabee, Jason et al. (2017) Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients. Clin Vaccine Immunol 24:
Wang, Xiaoqiu; Wu, Wenxin; Zhang, Wei et al. (2017) RIG-I overexpression decreases mortality of cigarette smoke exposed mice during influenza A virus infection. Respir Res 18:166
Keshari, Ravi Shankar; Silasi, Robert; Popescu, Narcis Ioan et al. (2017) Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli sepsis. Proc Natl Acad Sci U S A :
Patel, Vineet I; Booth, J Leland; Duggan, Elizabeth S et al. (2017) Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets. J Immunol 198:1183-1201
Patel, Vineet Indrajit; Metcalf, Jordan Patrick (2016) Identification and characterization of human dendritic cell subsets in the steady state: a review of our current knowledge. J Investig Med 64:833-47

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