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Antimicrobial Agents and Chemotherapy, November 2009, p. 4860-4868, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.01269-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Radiolabeled Antibodies to Bacillus anthracis Toxins Are Bactericidal and Partially Therapeutic in Experimental Murine Anthrax{triangledown}

Johanna Rivera,1 Antonio S. Nakouzi,1 Alfred Morgenstern,4 Frank Bruchertseifer,4 Ekaterina Dadachova,1,2,{dagger} and Arturo Casadevall1,3,{dagger}*

Department of Microbiology and Immunology,1 Department of Nuclear Medicine,2 Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461,3 European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany4

Received 22 September 2008/ Returned for modification 20 October 2008/ Accepted 14 August 2009

Bacillus anthracis is a powerful agent for use in biological warfare, and infection with the organism is associated with a high rate of mortality, underscoring the need for additional effective therapies for anthrax. Radioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver a microbicidal radioactive nuclide to a site of infection. RIT has proven therapeutic in experimental models of viral, bacterial, and fungal infections; but it is not known whether this approach can successfully employ toxin binding monoclonal antibodies (MAbs) for diseases caused by toxigenic bacteria. Indirect immunofluorescence studies with MAbs to protective antigen (MAbs 7.5G {gamma}2b and 10F4 {gamma}1) and lethal factor (MAb 14FA {gamma}2b) revealed the 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, 213Bi was more efficient than 188Re in mediating microbicidal activity against B. anthracis. The administration of MAbs [213Bi]10F4 {gamma}1 and [213Bi]14FA {gamma}2b prolonged the survival of A/JCr mice infected with B. anthracis Sterne bacterial cells but not B. anthracis Sterne spores. These results indicate that RIT with MAbs that target B. anthracis toxin components can be used to treat experimental anthrax infection and suggest that toxigenic bacteria may be targeted with radiolabeled MAbs.

* Corresponding author. Mailing address: Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-3730. Fax: (718) 430-8968. E-mail: casadeva{at}aecom.yu.edu

{triangledown} Published ahead of print on 24 August 2009.

{dagger} E.D. and A.C. share senior authorship.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4860-4868, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.01269-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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