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 #
5U19AI062629-09
Application #
8320322
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
2012-09-01
Budget End
2013-08-31
Support Year
9
Fiscal Year
2012
Total Cost
$2,776,772
Indirect Cost
$469,233
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
077333797
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Liu, Ke; Kurien, Biji T; Zimmerman, Sarah L et al. (2016) X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome. Arthritis Rheumatol 68:1290-300
Garman, Lori; Smith, Kenneth; Muns, Emily E et al. (2016) Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination. Clin Vaccine Immunol 23:664-71
Hu, Zihua; Jiang, Kaiyu; Frank, Mark Barton et al. (2016) Complexity and Specificity of the Neutrophil Transcriptomes in Juvenile Idiopathic Arthritis. Sci Rep 6:27453
Devera, T Scott; Lang, Gillian A; Lanis, Jordi M et al. (2016) Memory B Cells Encode Neutralizing Antibody Specific for Toxin B from the Clostridium difficile Strains VPI 10463 and NAP1/BI/027 but with Superior Neutralization of VPI 10463 Toxin B. Infect Immun 84:194-204
McMurtrey, Curtis; Trolle, Thomas; Sansom, Tiffany et al. (2016) Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove. Elife 5:
Wu, Wenxin; Zhang, Wei; Booth, J Leland et al. (2016) Human primary airway epithelial cells isolated from active smokers have epigenetically impaired antiviral responses. Respir Res 17:111
Booth, J Leland; Duggan, Elizabeth S; Patel, Vineet I et al. (2016) Bacillus anthracis spore movement does not require a carrier cell and is not affected by lethal toxin in human lung models. Microbes Infect 18:615-626
Smith, Kenneth; Shah, Hemangi; Muther, Jennifer J et al. (2016) Antigen nature and complexity influence human antibody light chain usage and specificity. Vaccine 34:2813-20
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
Kovats, S; Turner, S; Simmons, A et al. (2016) West Nile virus-infected human dendritic cells fail to fully activate invariant natural killer T cells. Clin Exp Immunol 186:214-226

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