Neutralizing antibody and functional mapping of Bacillus anthracis protective antigen—The first step toward a rationally designed anthrax vaccine |
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| Institution: | 1. Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA;2. Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA;3. Department of Clinic Laboratory, Second Xiangya Hospital, Central South University, 139 Renmin Middle Rd., Changsha, Hunan 410011, China;1. Key Laboratory of Experimental Marine Biology at the Institute of Oceanology of the Chinese Academy of Sciences and Laboratory of Marine Biology and Biotechnology of the Qingdao National Laboratory for Marine Science and Technology, Nanhai Road 7, Qingdao 266071, China;2. University of Chinese Academy of Sciences, Yuquan Road 19A, Beijing 100049, China;1. School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland, Australia;2. Biotechnology Centre, Universidad San Sebastián, Concepción, Chile;3. Institute of Integrative Biology, University of Liverpool, United Kingdom;4. Transplant Immunology Laboratory, Royal Liverpool University Hospital & School of Infection and Host Defence University of Liverpool, United Kingdom;5. School of Information Technology and Electrical Engineering, University of Queensland, Queensland 4072, Australia;1. Departamento de Genética, Facultad de CC. Biológicas, Universidad de Valencia, Burjassot, Spain |
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| Abstract: | Anthrax is defined by the Centers for Disease Control and Prevention as a Category A pathogen for its potential use as a bioweapon. Current prevention treatments include Anthrax Vaccine Adsorbed (AVA). AVA is an undefined formulation of Bacillus anthracis culture supernatant adsorbed to aluminum hydroxide. It has an onerous vaccination schedule, is slow and cumbersome to produce and is slightly reactogenic. Next-generation vaccines are focused on producing recombinant forms of anthrax toxin in a well-defined formulation but these vaccines have been shown to lose potency as they are stored. In addition, studies have shown that a proportion of the antibody response against these vaccines is focused on non-functional, non-neutralizing regions of the anthrax toxin while some essential functional regions are shielded from eliciting an antibody response. Rational vaccinology is a developing field that focuses on designing vaccine antigens based on structural information provided by neutralizing antibody epitope mapping, crystal structure analysis, and functional mapping through amino acid mutations. This information provides an opportunity to design antigens that target only functionally important and conserved regions of a pathogen in order to make a more optimal vaccine product. This review provides an overview of the literature related to functional and neutralizing antibody epitope mapping of the Protective Antigen (PA) component of anthrax toxin. |
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| Keywords: | Anthrax Protective antigen Neutralizing antibody mapping Functional mapping Rational vaccine design |
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