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Infection and Immunity, July 2001, p. 4509-4515, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4509-4515.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Protection against Anthrax Lethal Toxin Challenge by Genetic Immunization with a Plasmid Encoding the Lethal Factor Protein

Brian M. Price,1 Adriane L. Liner,1 Sukjoon Park,2,dagger Stephen H. Leppla,2 Alfred Mateczun,3 and Darrell R. Galloway1,*

Department of Microbiology, The Ohio State University, Columbus, Ohio 43017-12921; Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892-43502; and Biological Defense Research Directorate, NMRC, Silver Spring, Maryland 209103

Received 22 December 2000/Returned for modification 7 February 2001/Accepted 2 April 2001

The ability of genetic vaccination to protect against a lethal challenge of anthrax toxin was evaluated. BALB/c mice were immunized via gene gun inoculation with eucaryotic expression vector plasmids encoding either a fragment of the protective antigen (PA) or a fragment of lethal factor (LF). Plasmid pCLF4 contains the N-terminal region (amino acids [aa] 10 to 254) of Bacillus anthracis LF cloned into the pCI expression plasmid. Plasmid pCPA contains a biologically active portion (aa 175 to 764) of B. anthracis PA cloned into the pCI expression vector. One-micrometer-diameter gold particles were coated with plasmid pCLF4 or pCPA or a 1:1 mixture of both and injected into mice via gene gun (1 µg of plasmid DNA/injection) three times at 2-week intervals. Sera were collected and analyzed for antibody titer as well as antibody isotype. Significantly, titers of antibody to both PA and LF from mice immunized with the combination of pCPA and pCLF4 were four to five times greater than titers from mice immunized with either gene alone. Two weeks following the third and final plasmid DNA boost, all mice were challenged with 5 50% lethal doses of lethal toxin (PA plus LF) injected intravenously into the tail vein. All mice immunized with pCLF4, pCPA, or the combination of both survived the challenge, whereas all unimmunized mice did not survive. These results demonstrate that DNA-based immunization alone can provide protection against a lethal toxin challenge and that DNA immunization against the LF antigen alone provides complete protection.

* Corresponding author. Mailing address: Department of Microbiology, The Ohio State University, Columbus, OH 43017-1292. Phone: (614) 292-3761. Fax: (614) 292-8120. E-mail: galloway.3{at}osu.edu.

dagger Present address: BioPort Corporation, Lansing, Mich.

Infection and Immunity, July 2001, p. 4509-4515, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4509-4515.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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