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Infection and Immunity, January 2007, p. 152-163, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01133-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Protective and Immunochemical Activities of Monoclonal Antibodies Reactive with the Bacillus anthracis Polypeptide Capsule{triangledown}

Thomas R. Kozel,1* Peter Thorkildson,1 Suzanne Brandt,1,{dagger} William H. Welch,2 Julie A. Lovchik,3 David P. AuCoin,1 Julpohng Vilai,1 and C. Rick Lyons3

Departments of Microbiology and Immunology,1 Biochemistry and Molecular Biology, University of Nevada School of Medicine, Reno, Nevada 89557,2 Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 871313

Received 19 July 2006/ Returned for modification 10 August 2006/ Accepted 6 October 2006

Bacillus anthracis is surrounded by a polypeptide capsule composed of poly-gamma-D-glutamic acid ({gamma}DPGA). In a previous study, we reported that a monoclonal antibody (MAb F26G3) reactive with the capsular polypeptide is protective in a murine model of pulmonary anthrax. The present study examined a library of six MAbs generated from mice immunized with {gamma}DPGA. Evaluation of MAb binding to the capsule by a capsular "quellung" type reaction showed a striking diversity in capsular effects. Most MAbs produced a rim type reaction that was characterized by a sharp increase followed directly by a decrease in refractive index at the capsular edge. Some MAbs produced a second capsular reaction well beneath the capsular edge, suggesting complexity in capsular architecture. Binding of MAbs to soluble {gamma}DPGA was assessed by a fluorescence perturbation assay in which a change in the MAb intrinsic fluorescence produced by ligand binding was used as a reporter for antigen-antibody interaction. The MAbs differed considerably in the complexity of the binding curves. MAbs producing rim type capsule reactions typically produced the more complex binding isotherms. Finally, the protective activity of the MAbs was compared in a murine model of pulmonary anthrax. One MAb was markedly less protective than the remaining five MAbs. Characteristics of the more protective MAbs included a relatively high affinity, an immunoglobulin G3 isotype, and a complex binding isotherm in the fluorescence perturbation assay. Given the relatively monotonous structure of {gamma}DPGA, the results demonstrate a striking diversity in the antigen binding behavior of {gamma}DPGA antibodies.

* Corresponding author. Mailing address: Department of Microbiology and Immunology/320, University of Nevada School of Medicine, Reno, NV 89557. Phone: (775) 784-4124. Fax: (775) 327-2332. E-mail: tkozel{at}medicine.nevada.edu.

{triangledown} Published ahead of print on 23 October 2006.

Editor: A. Casadevall

{dagger} Present address: Earle A. Chiles Research Institute, Veterans Affairs Medical Center, 3710 SW US Vet. Hosp. Rd., Bldg 103/E146, Portland, OR 97201.

Infection and Immunity, January 2007, p. 152-163, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01133-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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