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Abstract
The potential use of Bacillus anthracis as a bioterrorism weapon threatens the security of populations globally, requiring the immediate availability of safe, efficient and easily delivered anthrax vaccine for mass vaccination. Extensive research efforts have been directed toward the development of recombinant subunit vaccines based on protective antigen (PA), the principal virulence factor of B. anthracis. Among the emerging technologies for the production of these vaccine antigens is our launch vector-based plant transient expression system. Using this system, we have successfully engineered, expressed, purified and characterized full-length PA (pp-PA83) in Nicotiana benthamiana plants using agroinfiltration. This plant-produced antigen elicited high toxin neutralizing antibody titers in mice and rabbits after two vaccine administrations with Alhydrogel. In addition, immunization with this vaccine candidate protected 100% of rabbits from a lethal aerosolized B. anthracis challenge. The vaccine effects were dose-dependent and required the presence of Alhydrogel adjuvant. In addition, the vaccine antigen formulated with Alhydrogel was stable and retained immunogenicity after two-week storage at 4°C, the conditions intended for clinical use. These results support the testing of this vaccine candidate in human volunteers and the utility of our plant expression system for the production of a recombinant anthrax vaccine.
Submitted
11/05/12
Accepted
11/21/12
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
The authors would like to thank MS Bioworks LLC. and Proteos, Inc. for performing peptide mapping and N-terminal sequencing, respectively. Covance Research Products Inc. and Southern Research Institute conducted the rabbit immunogenicity and challenge studies, respectively. The authors would like to thank Robert Stevens and Rebecca Snow for technical support and Dr. Natasha Kushnir for editorial assistance. This project was supported by grants from the Naval Medical Research Center and the Defense Threat Reduction Agency (contract number HDTRA1-09-C-0049).
