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Toxins 2015, 7(7), 2371-2384; doi:10.3390/toxins7072371

Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge

1
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
2
Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
3
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Shihui Liu
Received: 21 May 2015 / Revised: 15 June 2015 / Accepted: 18 June 2015 / Published: 25 June 2015
(This article belongs to the Collection Anthrax Toxins)
View Full-Text   |   Download PDF [500 KB, uploaded 25 June 2015]   |  

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. View Full-Text
Keywords: Bacillus anthracis; lethal toxin; protective antigen; neutralizing antibody; troponin Bacillus anthracis; lethal toxin; protective antigen; neutralizing antibody; troponin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Devera, T.S.; Prusator, D.K.; Joshi, S.K.; Ballard, J.D.; Lang, M.L. Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge. Toxins 2015, 7, 2371-2384.

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