Open AccessMonoclonal antibodies directed against protective antigen of Bacillus anthracis enhance lethal toxin activity in vivo
Author(s) -
Little Stephen F.,
Webster Wendy M.,
Fisher Diana E.
Publication year - 2011
Publication title -
fems immunology & medical microbiology
Language(s) - English
Resource type - Journals
eISSN - 1574-695X
pISSN - 0928-8244
DOI - 10.1111/j.1574-695x.2011.00782.x
Subject(s) - bacillus anthracis , anthrax toxin , biology , monoclonal antibody , toxin , cytotoxicity , in vivo , microbiology and biotechnology , in vitro , antibody , antigen , cytotoxic t cell , immunology , biochemistry , recombinant dna , bacteria , fusion protein , genetics , gene
Protective antigen (PA) from Bacillus anthracis binds to cellular receptors, combines with lethal factor (LF) forming lethal toxin (LeTx), and facilitates the translocation of LF into the cytosol. LeTx is cytotoxic for J774A.1 cells, a murine macrophage cell line, and causes death of Fisher 344 rats when injected intravenously. PA is also the major protective component in anthrax vaccines. Antibody‐dependent enhancement has been reported for several viral diseases, a bacterial infection, and for B. anthracis LeTx in vitro cytotoxicity. Further screening of our 73 PA monoclonal antibodies (mAbs) identified a total of 17 PA mAbs that enhanced in vitro cytotoxicity at suboptimal concentrations of LeTx. A competitive binding enzyme‐linked immunosorbent assay showed that these 17 PA mAbs identified eight different antigenic regions on PA. Eight of the 17 PA mAbs that enhanced LeTx in vitro cytoxicity were examined for their activity in vivo . Of the eight mAbs that were injected intravenously with a sublethal concentration of LeTx into male Fisher 344 rats, four mAbs enhanced the lethality of LeTx and resulted in the death of animals, whereas control animals did not succumb to intoxication. This is the first demonstration that PA mAbs can enhance LeTx intoxication in vivo .