title: A plant-produced protective antigen vaccine confers protection in rabbits against a lethal aerosolized challenge with Bacillus anthracis Ames spores.
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.
authors: 1Fraunhofer USA Center for Molecular Biotechnology; Newark, DE USA.
authors: Jessica A
authors: JA
authors: Chichester
authors: Slobodanka D
authors: SD
authors: Manceva
authors: Amy
authors: A
authors: Rhee
authors: Megan V
authors: MV
authors: Coffin
authors: Konstantin
authors: K
authors: Musiychuk
authors: Vadim
authors: V
authors: Mett
authors: Moneim
authors: M
authors: Shamloul
authors: Joey
authors: J
authors: Norikane
authors: Stephen J
authors: SJ
authors: Streatfield
authors: Vidadi
authors: V
authors: Yusibov
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000336:Aerosols; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D004195:Disease Models, Animal; D019570:Inhalation Exposure; D008807:Mice, Inbred BALB C; D030821:Plants, Genetically Modified / Q000235:genetics; D011817:Rabbits; D016019:Survival Analysis; D014026:Nicotiana / Q000235:genetics; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000336:Aerosols; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C030325:anthrax toxin; D000536:Aluminum Hydroxide
keywords: Anthrax; plant expression system; protective antigen; recombinant antigen; subunit vaccine