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Clinical and Vaccine Immunology, November 2008, p. 1737-1741, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00081-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Role of the N-Terminal Amino Acid of Bacillus anthracis Lethal Factor in Lethal Toxin Cytotoxicity and Its Effect on the Lethal Toxin Neutralization Assay {triangledown}

Anita Verma, Leslie Wagner, Scott Stibitz, Nga Nguyen, Flor Guerengomba, and Drusilla L. Burns*

Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892

Received 3 March 2008/ Returned for modification 22 April 2008/ Accepted 9 September 2008

The cytotoxic activity of lethal factor (LF), a critical reagent used in the cell-based lethal toxin neutralization assay to assess anthrax vaccines, was shown to depend on the identity of its N-terminal amino acid, which plays a role in the targeting of LF to the proteasome for degradation. These results demonstrate that care must be taken to ensure that LF preparations used in standardized cell-based assays are not altered at their N-terminal ends.


* Corresponding author. Mailing address: CBER, FDA HFM-434, Building 29, Room 130, 8800 Rockville Pike, Bethesda, MD 20892. Phone: (301) 402-3553. Fax: (301) 402-2776. E-mail: drusilla.burns{at}fda.hhs.gov

{triangledown} Published ahead of print on 24 September 2008.


Clinical and Vaccine Immunology, November 2008, p. 1737-1741, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00081-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.