文章基本信息

标题：Anthrax LFn-PA Hybrid Antigens: Biochemistry, Immunogenicity, and Protection Against Lethal Ames Spore Challenge in Rabbits
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作者：Qin Li ; Kristina K. Peachman ; Laurie Sower 等
期刊名称：Open Vaccine Journal
电子版ISSN：1875-0354
出版年度：2009
卷号：2
期号：1
页码：92-99
DOI：10.2174/1875035401002010092
出版社：Bentham open
摘要：
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.