Anthrax LFn-PA Hybrid Antigens: Biochemistry, Immunogenicity, and Protection Against Lethal Ames Spore Challenge in Rabbits

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...

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Bibliographic Details
Published in:The open vaccine journal 2009, Vol.2 (1), p.92-99
Main Authors: Li, Qin, Peachman, Kristina K, Sower, Laurie, Leppla, Stephen H, Shivachandra, Sathish B, Matyas, Gary R, Peterson, Johnny W, Alving, Carl R, Rao, Mangala, Rao, Venigalla B
Format: Article
Language:English
Subjects:
Anthrax
Antibodies
Bacillus anthracis
Escherichia coli
furin
Hybrids
Immunity
Immunogenicity
Lethal factor
protective antigen
Spores
Toxins
Translocation
Vaccines
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Summary: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 LD(50) dose of Bacillus anthracis Ames strain spores.
ISSN:1875-0354
1875-0354
DOI:10.2174/1875035400902010092