Neutralizing Monoclonal Antibody to Edema Toxin and Its Effect on Murine Anthrax

作者: Lisa Winterroth , Johanna Rivera , Antonio S. Nakouzi , Ekaterina Dadachova , Arturo Casadevall

DOI: 10.1128/IAI.01101-09

关键词:

摘要: Edema factor (EF) is a component of an anthrax toxin that functions as adenylate cyclase. Numerous monoclonal antibodies (MAbs) have been reported for the other Bacillus anthracis components, but relatively few to EF studied. We report generation six murine hybridoma lines producing two IgM and four IgG1 MAbs EF. Of MAbs, only one neutralized EF, assayed by increase in cyclic AMP (cAMP) production Chinese hamster ovary (CHO) cells. Analysis variable gene elements revealed single neutralizing MAb had different binding site than others. There was no competition between nonneutralizing IgG indicative specificity. MAb-based capture enzyme-linked immunosorbent assay (ELISA) detected liver lysates from mice infected with B. Sterne 34F2. Administration A/JCr lethally strain significant effect on median time death, treated were more likely survive infection. Combining subprotective dose protective antigen (PA) prolonged mean death mice, suggesting neutralization PA could produce synergistic beneficial effects. In summary, results our study literature observations suggest majority Abs are nonneutralizing, has some epitopes can be targeted humoral response generate useful may contribute defense against anthrax.

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