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Neutralizing monoclonal antibody to edema toxin and its effect on murine anthrax. | LitMetric

Neutralizing monoclonal antibody to edema toxin and its effect on murine anthrax.

Infect Immun

Departments of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.

Published: June 2010

AI Article Synopsis

  • * The researchers created six murine hybridoma lines that produced two IgM and four IgG1 MAbs, with only one IgM showing the ability to neutralize EF by increasing cyclic AMP production in cells.
  • * Mice treated with the neutralizing IgM had a higher survival chance during anthrax infection, and combining it with another antibody targeting protective antigen (PA) improved survival times, indicating potential for these antibodies to work together in anthrax defense.

Article Abstract

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

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876569PMC
http://dx.doi.org/10.1128/IAI.01101-09DOI Listing

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