TY - JOUR
T1 - Anthrax LFn-PA hybrid antigens
T2 - Biochemistry, immunogenicity, and protection against lethal Ames spore challenge in rabbits
AU - Li, Qin
AU - Peachman, Kristina K.
AU - Sower, Laurie
AU - Leppla, Stephen H.
AU - Shivachandra, Sathish B.
AU - Matyas, Gary R.
AU - Peterson, Johnny W.
AU - Alving, Carl R.
AU - Rao, Mangala
AU - Rao, Venigalla B.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.2174/1875035400902010092
DO - 10.2174/1875035400902010092
M3 - Article
AN - SCOPUS:77953435305
SN - 1875-0354
VL - 2
SP - 92
EP - 99
JO - Open Vaccine Journal
JF - Open Vaccine Journal
ER -