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. 2015 Jul 24;10(7):e0130952.
doi: 10.1371/journal.pone.0130952. eCollection 2015.

Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection

Matthew D Reed  1 , Julie A Wilder  1 , William M Mega  1 , Julie A Hutt  1 , Philip J Kuehl  1 , Michelle W Valderas  1 , Lawrence L Chew  2 , Bertrand C Liang  2 , Charles H Squires  2
Affiliations

Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax Infection

Matthew D Reed et al. PLoS One. .

Abstract

Protective antigen (PA), one of the components of the anthrax toxin, is the major component of human anthrax vaccine (Biothrax). Human anthrax vaccines approved in the United States and Europe consist of an alum-adsorbed or precipitated (respectively) supernatant material derived from cultures of toxigenic, non-encapsulated strains of Bacillus anthracis. Approved vaccination schedules in humans with either of these vaccines requires several booster shots and occasionally causes adverse injection site reactions. Mutant derivatives of the protective antigen that will not form the anthrax toxins have been described. We have cloned and expressed both mutant (PA SNKE167-ΔFF-315-E308D) and native PA molecules recombinantly and purified them. In this study, both the mutant and native PA molecules, formulated with alum (Alhydrogel), elicited high titers of anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both mutant and native PA vaccine preparations protected rabbits from lethal, aerosolized, B. anthracis spore challenge subsequent to two immunizations at doses of less than 1 μg.

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Conflict of interest statement

Competing Interests: This work was performed at LBERI under Pfenex Inc.’s prime U.S. Health and Human Services (HHS) Biomedical Advanced Research Development Authority (BARDA) technology contract HHS0100201000045C. BCL is and LLC and CHS were employees of Pfenex Inc. Subsequent to completion of the enclosed work, LLC was employed by PaxVax Corp. and CHS was employed by Leidos Life Sciences. There are no patents, products in development or marketed products to declare as a result of this work. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Ig anti-PA ELISA values (μg/mL).
(A) generated from vaccinated wild type and (B) mutant rPA (geometric mean with error bars representing the 95% confidence interval).
Fig 2
Fig 2. rPA antibody-specific Toxin Neutralization Assay (TNA) and ED50 values (μg/mL).
(A) generated from vaccinated wild type and (B) mutant rPA (geometric mean with error bars representing the 95% confidence interval).
Fig 3
Fig 3. Kaplan-Meier Survival Curve of vaccinated, unvaccinated control, and sham vaccinated control rabbits.
Fig 4
Fig 4. Recovery of B. anthracis from Select Tissues of vaccinated, unvaccinated control, and sham vaccinated control rabbits.
See this image and copyright information in PMC

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