Anthrax continues to be one of the most commonly identified potential risks for bioterrorism attacks. Over the past four funding years, our group has collected samples from over 800 military personnel vaccinated with Absorbed Vaccine Anthrax (AVA) in collaboration with the Harley project. We were stunned to learn that ess than half of vaccinated individuals have antibodies able to significantly inhibit in vitro macrophage killing by anthrax Lethal Toxin (LT) (a standard measure of in vitro protection), even though most vaccinees make antibodies against protective antigen (PA). We have identified key humoral epitopes of the responses to PA [1] and lethal factor (LF) [2] that correlate with in vitro protection. Select humoral epitope responses able to protect mice from in vivo LT are found. Our ongoing work characterizes key LF epitopes that are produced in approximately 10% of currently vaccinated individuals to identify additional potential immunotherapeutics or ways to improve the vaccine immune response. Preliminary data suggest that CD4* responses against key vaccine components can be identified. We will build on these advances to understand critical reasons why so many individuals apparently have inadequate responses to the current vaccine and to identify those immune responses that are essential for protection. Our team will build on key humoral epitopes already identified and use our extensive expertise in protein chemistry, epitope mapping and confirmation, molecular modeling, animal immunization, and T cell immunology to identify the common B cell targets of edema factor (EF) and test combinations of peptide epitopes for protection in vivo and in vitro. Previously collected samples from over 800 individuals will allow us to examine Bacillus anthracis T cell antigenic targets of toxin components which correlate with protection. Baboon samples from the Kurosawa Technical Project before and after vaccination, toxin challenge and spore challenge will allow further definition of the minimal necessary protective response and evaluation of the temporal evolution of anthrax specific B and T cell responses. In collaboration with the Wilson Technical Project we will test and characterize fully human neutralizing monoclonal antibodies generated after AVA vaccination. Other work focuses on understanding clinical and cellular correlates of protection after AVA vaccination. This project will provide understanding of the key aspects of protective immune responses to anthrax toxins and allow generation of better vaccines, immunotherapeutics and rapid screening tests for detection.

Public Health Relevance

Bacillus anthracis remains a major bioterrorist threat. Current vaccination strategies are only utilized by the US military due to adverse event potential, cumbersome vaccination schedule with limited compliance, production problems and questions regarding real-world protection. Improved understanding of the necessary minimal immune responses for protection again anthrax toxins would allow generation of better vaccines, immunotherapeutics and rapid methods to detect exposure.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-KS-I)
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Oklahoma Medical Research Foundation
Oklahoma City
United States
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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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