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

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 plasniids encoding either a fragnient of the protective antigen (PA) or a fragnient of lethal factor (LF). Pl...

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Bibliographic Details
Main Authors: Price, Brian M, Liner, Adriane L, Park, Sukjoon, Leppla, Stephen H, Mateczun, Alfred, Galloway, Darrell R
Format: Report
Language:English
Subjects:
ANTHRAX
ANTIBODIES
ANTIGENS
BACILLUS ANTHRACIS
BACTERIAL TOXINS
BOOST PHASE
CLONES
CODING
DEOXYRIBONUCLEIC ACIDS
Genetic Engineering and Molecular Biology
GENETICS
IMMUNIZATION
LETHALITY
LOW FREQUENCY
Medicine and Medical Research
PLASMIDS
PROTEINS
REPRINTS
TAIL ASSEMBLIES
Toxicology
TOXINS AND ANTITOXINS
VEINS
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Summary: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 plasniids encoding either a fragnient of the protective antigen (PA) or a fragnient of lethal factor (LF). Plasniid pCLF4 contains the N-terniinal region (aniino acids [aa] 10 to 254) of Baclllus anthracis LF cloned into the pCI expression plasniid. Plasniid pCPA contains a biologically active portion (aa 175 to 764) of B. anthracis PA cloned into the pCI expression vector. One-rnicrorneter-diarneter gold particles were coated with plasniid pCLF4 or pCPA or a 1:1 niixture of both and injected into niice via gene gun (1 %%g of plasniid DNAlinjection) three tinies 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 froni niice ininiunized with the conibination of pCPA and pCLF4 were four to five tinies greater than titers froni niice ininiunized with either gene alone. Two weeks following the third and final plasniid DNA boost, all niice were challenged with 5 50% lethal doses of lethal toxin (PA plus LF) ii'jected intravenously into the tail vein. All niice ininiunized with pCLF4, pCPA, or the conibination of both survived the challenge, whereas all unininiunized niice did not survive. These results denionstrate that DNA-based ininiunization alone can provide protection against a lethal toxin challenge and that DNA ininiunization against the LF antigen alone provides coniplete protection. Published in Infection and Immunity, v69 n7 p4509-4515, Jul 2001.