title: Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge.
abstract: Protective immunity against anthrax is inferred from measurement of vaccine antigen-specific neutralizing antibody titers in serum samples. In animal models, in vivo challenges with toxin and/or spores can also be performed. However, neither of these approaches considers toxin-induced damage to specific organ systems. It is therefore important to determine to what extent anthrax vaccines and existing or candidate adjuvants can provide organ-specific protection against intoxication. We therefore compared the ability of Alum, CpG DNA and the CD1d ligand α-galactosylceramide (αGC) to enhance protective antigen-specific antibody titers, to protect mice against challenge with lethal toxin, and to block cardiotoxicity and hepatotoxicity. By measurement of serum cardiac Troponin I (cTnI), and hepatic alanine aminotransferase (ALT), and aspartate aminotransferase (AST), it was apparent that neither vaccine modality prevented hepatic intoxication, despite high Ab titers and ultimate survival of the subject. In contrast, cardiotoxicity was greatly diminished by prior immunization. This shows that a vaccine that confers survival following toxin exposure may still have an associated morbidity. We propose that organ-specific intoxication should be monitored routinely during research into new vaccine modalities.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. tscottdev@gmail.com.
authors.forename: T Scott
authors.initials: TS
authors.lastname: Devera
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. dawn-prusator@ouhsc.edu.|Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. dawn-prusator@ouhsc.edu.
authors.forename: Dawn K
authors.initials: DK
authors.lastname: Prusator
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. skjoshi@odu.edu.|Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA. skjoshi@odu.edu.
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. jimmy-ballard@ouhsc.edu.
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Ballard
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. mark-lang@ouhsc.edu.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Lang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000881:Anthrax / Q000150:complications* / Q000276:immunology; D022122:Anthrax Vaccines / Q000276:immunology / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D066126:Cardiotoxicity / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D019210:Troponin I / Q000097:blood
chemical_list: D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D019210:Troponin I; C030325:anthrax toxin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Bacillus anthracis; lethal toxin; neutralizing antibody; protective antigen; troponin