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|Title:||Radiolabeled Antibodies to Bacillus Anthracis Toxins are Bactericidal and Partially Therapeutic in Experimental Murine Anthrax|
|Authors:||RIVERA J.; NAKOUZI A.s.; MORGENSTERN Alfred; BRUCHERTSEIFER Frank; DADACHOVA E.|
|Citation:||ANTIMICROBIAL AGENTS AND CHEMOTHERAPY vol. 53 no. 11 p. 4680-4688|
|Publisher:||AMER SOC MICROBIOLOGY|
|Type:||Articles in periodicals and books|
|Abstract:||Bacillus anthracis is a powerful agent for biological warfare associated with high mortality underscoring the need for additional effective therapies for anthrax. Radioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen (Ag)-antibody (Ab) interaction to deliver a microbicidal radioactive nuclide to a site of infection. RIT has proven therapeutic in experimental models of viral, bacterial and fungal infection but it is not known whether this approach can successfully employ toxin binding mAbs for diseases caused by toxigenic bacteria. Indirect immunofluorescence (IF) studies with mAbs to protective antigen (PA; 7.5G ¿2b and 10F4 ¿1) and lethal factor (LF; mAb 14FA ¿2b) revealed surface expression of toxins on bacterial cells. Scatchard analysis of mAbs revealed high binding constants and numerous binding sites on the bacterial surface. To investigate the microbicidal properties of these mAbs, our group radiolabeled mAbs with either 188Re or 213Bi. In vitro, 213 Bi was more efficient than 188 Re in mediating microbicidal activity against B. anthracis. Administration of mAbs 213Bi-10F4 and 21332 Bi-14FA prolonged survival of A/JCr mice infected with B. anthracis Sterne bacterial cells but not B. anthracis Sterne spores. These results indicate that RIT can be used to treat experimental anthrax infection using mAbs that target B. anthracis toxin components and suggest that toxigenic bacteria may be targeted with radiolabeled mAbs.|
|JRC Directorate:||Nuclear Safety and Security|
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