Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge
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 spec...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-06-01
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| Series: | Toxins |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6651/7/7/2371 |
| _version_ | 1811184712255799296 |
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| author | T. Scott Devera Dawn K. Prusator Sunil K. Joshi Jimmy D. Ballard Mark L. Lang |
| author_facet | T. Scott Devera Dawn K. Prusator Sunil K. Joshi Jimmy D. Ballard Mark L. Lang |
| author_sort | T. Scott Devera |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:18:06Z |
| format | Article |
| id | doaj.art-6e95c6f42d864c0c892ab209ad93b62f |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T13:18:06Z |
| publishDate | 2015-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-6e95c6f42d864c0c892ab209ad93b62f2022-12-22T04:22:20ZengMDPI AGToxins2072-66512015-06-01772371238410.3390/toxins7072371toxins7072371Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin ChallengeT. Scott Devera0Dawn K. Prusator1Sunil K. Joshi2Jimmy D. Ballard3Mark L. Lang4Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAProtective 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.http://www.mdpi.com/2072-6651/7/7/2371Bacillus anthracislethal toxinprotective antigenneutralizing antibodytroponin |
| spellingShingle | T. Scott Devera Dawn K. Prusator Sunil K. Joshi Jimmy D. Ballard Mark L. Lang Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge Toxins Bacillus anthracis lethal toxin protective antigen neutralizing antibody troponin |
| title | Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge |
| title_full | Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge |
| title_fullStr | Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge |
| title_full_unstemmed | Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge |
| title_short | Immunization of Mice with Anthrax Protective Antigen Limits Cardiotoxicity but Not Hepatotoxicity Following Lethal Toxin Challenge |
| title_sort | immunization of mice with anthrax protective antigen limits cardiotoxicity but not hepatotoxicity following lethal toxin challenge |
| topic | Bacillus anthracis lethal toxin protective antigen neutralizing antibody troponin |
| url | http://www.mdpi.com/2072-6651/7/7/2371 |
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