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 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.
Li
Qin
Q
Department of Biology, 103 McCort Ward Hall, The Catholic University of America, 620 Michigan Ave., NE, Washington, DC 20064, USA.
Peachman
Kristina K
KK
Sower
Laurie
L
Leppla
Stephen H
SH
Shivachandra
Sathish B
SB
Matyas
Gary R
GR
Peterson
Johnny W
JW
Alving
Carl R
CR
Rao
Mangala
M
Rao
Venigalla B
VB
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