Anthrax LFn-PA hybrid antigens: Biochemistry, immunogenicity, and protection against lethal Ames spore challenge in rabbits

Qin Li, Kristina K. Peachman, Laurie Sower, Stephen H. Leppla, Sathish B. Shivachandra, Gary R. Matyas, Johnny W. Peterson, Carl R. Alving, Mangala Rao, Venigalla B. Rao

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

We describe a novel hybrid anthrax toxin approach that incorporates multiple components into a single vaccine product. The key domains of protective antigen (PA) and lethal factor (LF) that may be critical for inducing protective immunity are combined into one recombinant molecule. Two LF N-terminal domain-PA hybrids, one with wild-type PA and another with furin cleavage-minus PA, were expressed in E. coli and purified in a native form. Both the hybrids bind to the extracellular domain of the host receptor, CMG2; the wild-type hybrid can be cleaved by furin exposing the LF interacting domain, allowing it to oligomerize into lethal toxin as well as translocation pore-like complexes. The hybrid antigens are immunogenic in Dutch-belted rabbits, eliciting strong PA-specific and LF-specific antibodies. However, the lethal toxin neutralizing antibody titers are 3-7 times lower than those elicited by PA-alum. The hybrid antigens conferred 100% (6/6) protection in rabbits challenged intranasally with a 100 LD50 dose of Bacillus anthracis Ames strain spores.

Original languageEnglish (US)
Pages (from-to)92-99
Number of pages8
JournalOpen Vaccine Journal
Volume2
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Immunology
  • Pharmaceutical Science
  • Drug Discovery

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    Li, Q., Peachman, K. K., Sower, L., Leppla, S. H., Shivachandra, S. B., Matyas, G. R., Peterson, J. W., Alving, C. R., Rao, M., & Rao, V. B. (2009). Anthrax LFn-PA hybrid antigens: Biochemistry, immunogenicity, and protection against lethal Ames spore challenge in rabbits. Open Vaccine Journal, 2, 92-99. https://doi.org/10.2174/1875035400902010092