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Infection and Immunity, December 2005, p. 8362-8368, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8362-8368.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Passive Protection against Anthrax by Using a High-Affinity Antitoxin Antibody Fragment Lacking an Fc Region

Robert Mabry,1,2 Mridula Rani,2 Robert Geiger,3 Gene B. Hubbard,3 Ricardo Carrion Jr,4 Kathleen Brasky,3 Jean L. Patterson,4 George Georgiou,2,5* and B. L. Iverson1,2*

Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas,1 Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas,2 Department of Comparative Medicine, Southwest Foundation for Biomedical Research, San Antonio, Texas,3 Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas,4 Department of Chemical Engineering and Biomedical Engineering, University of Texas at Austin, Austin, Texas5

Received 13 July 2005/ Returned for modification 16 August 2005/ Accepted 4 September 2005

Passive immunization has been successfully employed for protection against bacterial and viral infections for over 100 years. Immunoglobulin Fc regions play a critical role in the clearance of bacterial pathogens by mediating antibody-dependent and complement-dependent cytotoxicity. Here we show that antibody fragments engineered to recognize the protective antigen component of the B. anthracis exotoxin with high affinity and conjugated to polyethylene glycol (PEG) for prolonged circulation half-life confer significant protection against inhalation anthrax despite their lack of Fc regions. The speed and lower manufacturing cost of bacterially expressed PEGylated antibody fragments could provide decisive advantages for anthrax prophylaxis. Importantly, our results suggest that PEGylated antibody fragments may represent a unique approach for mounting a rapid therapeutic response to emerging pathogen infections.

* Corresponding author. Mailing address for George Georgiou: Department of Chemical Engineering and Biomedical Engineering, University of Texas at Austin, 1 University Station, Austin, TX 78712. Phone:(512) 471-6975. Fax: (512) 471-7963. E-mail: gg{at}che.utexas.edu. Mailing address for B. L. Iverson: Department of Chemistry and Biochemistry, University of Texas at Austin, 1 University Station, Austin, TX 78712. Phone: (512) 471-5053. Fax: (512) 471-8615. E-mail: biverson{at}mail.utexas.edu.

Editor: J. D. Clements

Infection and Immunity, December 2005, p. 8362-8368, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8362-8368.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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