3.9 Article

Monoclonal antibodies directed against protective antigen of Bacillus anthracis enhance lethal toxin activity in vivo

期刊

FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY
卷 62, 期 1, 页码 11-22

出版社

WILEY-BLACKWELL
DOI: 10.1111/j.1574-695X.2011.00782.x

关键词

monoclonal antibodies; antibody-dependent enhancement; in vivo; anthrax lethal toxin

资金

  1. DTRA [92230]
  2. US Army Medical Research and Materiel Command [02-4-CC-009]

向作者/读者索取更多资源

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.

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