This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bacillus anthracis spores can cause significant morbidity and mortality if released into the environment. There is a need for both an effective vaccine as well as targeted immunotherapeutic agents. The currently licensed vaccine requires six vaccinations, annual boosters, and has been associated with serious adverse events. Thus there has been a major effort made to develop an improved vaccination strategy which can generate lasting protective immunity with reduced vaccinations. Dr. James'laboratory has been working to identify the major humoral targets of B. anthracis that provide protection. Human monoclonal antibodies were previously generated from individuals who received the anthrax vaccine. Each of these monoclonal antibodies has previously been characterized in both in vitro and in vivo toxin neutralization assays as well as by linear epitope and protease fragment mapping studies. Multiple functionally informative anti-PA monoclonal antibodies were identified. However, the structural epitopes recognized by these functionally informative monoclonal antibodies remained unclear. These monoclonal antibodies apparently recognized conformational epitopes rather than the linear peptide epitopes of protective antigen. The goal of this study was to define the protective antigen structural determinants that were specifically recognized by the functionally informative monoclonal anti-PA antibodies. Using the three dimensional structure of anthrax PA as a guide, different domains of PA will be cloned as recombinant fusion proteins. These PA subdomain containing fusion proteins will then be expressed and used in protein binding assays to define which PA domains are required for anti-PA monoclonal antibody binding. The results of these studies will identify which domains of PA are the best targets for generating protective immune responses through vaccination.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016478-10
Application #
8167527
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2010-04-01
Project End
2011-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
10
Fiscal Year
2010
Total Cost
$13,943
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
878648294
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
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
Wetherill, Marianna S; Williams, Mary B; Gray, Karen A (2017) SNAP-Based Incentive Programs at Farmers' Markets: Adaptation Considerations for Temporary Assistance for Needy Families (TANF) Recipients. J Nutr Educ Behav 49:743-751.e1
Hannafon, Bethany N; Trigoso, Yvonne D; Calloway, Cameron L et al. (2016) Plasma exosome microRNAs are indicative of breast cancer. Breast Cancer Res 18:90
Wilson, Kevin R; Cannon-Smith, Desiray J; Burke, Benjamin P et al. (2016) Synthesis and structural studies of two pyridine-armed reinforced cyclen chelators and their transition metal complexes. Polyhedron 114:118-127
Trigoso, Yvonne D; Evans, Russell C; Karsten, William E et al. (2016) Cloning, Expression, and Purification of Histidine-Tagged Escherichia coli Dihydrodipicolinate Reductase. PLoS One 11:e0146525
Khandaker, Morshed; Riahinezhad, Shahram; Sultana, Fariha et al. (2016) Peen treatment on a titanium implant: effect of roughness, osteoblast cell functions, and bonding with bone cement. Int J Nanomedicine 11:585-94
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
Jones, Donald G; Wilson, Kevin R; Cannon-Smith, Desiray J et al. (2015) Synthesis, structural studies, and oxidation catalysis of the late-first-row-transition-metal complexes of a 2-pyridylmethyl pendant-armed ethylene cross-bridged cyclam. Inorg Chem 54:2221-34
Wetherill, Marianna S; Gray, Karen A (2015) Farmers' markets and the local food environment: identifying perceived accessibility barriers for SNAP consumers receiving temporary assistance for needy families (TANF) in an urban Oklahoma community. J Nutr Educ Behav 47:127-33.e1
Butler, Noah S; Kulu, Divine I (2015) The regulation of T follicular helper responses during infection. Curr Opin Immunol 34:68-74

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