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.
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.
|Morris, D L; Fernando, M M A; Taylor, K E et al. (2014) MHC associations with clinical and autoantibody manifestations in European SLE. Genes Immun 15:210-7|
|Garman, Lori; Smith, Kenneth; Farris, A Darise et al. (2014) Protective antigen-specific memory B cells persist years after anthrax vaccination and correlate with humoral immunity. Toxins (Basel) 6:2424-31|
|Garman, Lori; Vineyard, Amanda J; Crowe, Sherry R et al. (2014) Humoral responses to independent vaccinations are correlated in healthy boosted adults. Vaccine 32:5624-31|
|Lupu, Florea; Keshari, Ravi S; Lambris, John D et al. (2014) Crosstalk between the coagulation and complement systems in sepsis. Thromb Res 133 Suppl 1:S28-31|
|Joshi, Sunil K; Lang, Mark L (2013) Fine tuning a well-oiled machine: Influence of NK1.1 and NKG2D on NKT cell development and function. Int Immunopharmacol 17:260-6|
|Lee, Benjamin C; Mayer, Chad L; Leibowitz, Caitlin S et al. (2013) Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy. Blood 122:803-6|
|Dumas, Eric K; Nguyen, Melissa L; Cox, Philip M et al. (2013) Stochastic humoral immunity to Bacillus anthracis protective antigen: identification of anti-peptide IgG correlating with seroconversion to Lethal Toxin neutralization. Vaccine 31:1856-63|
|Sun, Dawei; Popescu, Narcis I; Raisley, Brent et al. (2013) Bacillus anthracis peptidoglycan activates human platelets through FcýýRII and complement. Blood 122:571-9|
|Chiu, Christopher; Wrammert, Jens; Li, Gui-Mei et al. (2013) Cross-reactive humoral responses to influenza and their implications for a universal vaccine. Ann N Y Acad Sci 1283:13-21|
|Smith, Kenneth; Muther, Jennifer J; Duke, Angie L et al. (2013) Fully human monoclonal antibodies from antibody secreting cells after vaccination with Pneumovaxýý23 are serotype specific and facilitate opsonophagocytosis. Immunobiology 218:745-54|
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