Immunization of mice with anthrax protective antigen limits cardiotoxicity but not hepatotoxicity following lethal toxin challenge

T. Scott Devera, Dawn K. Prusator, Sunil K. Joshi, Jimmy D. Ballard, Mark L. Lang

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2371-2384
Number of pages14
JournalToxins
Volume7
Issue number7
DOIs
StatePublished - Jun 25 2015

Keywords

  • Bacillus anthracis
  • Lethal toxin
  • Neutralizing antibody
  • Protective antigen
  • Troponin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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