title: Stability and pre-formulation development of a plant-produced anthrax vaccine candidate.
abstract: Second generation anthrax vaccines focus on the use of recombinant protective antigen (rPA) to elicit a strong, toxin neutralizing antibody responses in immunized subjects. The main difference between the rPA vaccines compared to the current licensed vaccine, anthrax vaccine absorbed (AVA), is the rPA vaccines are highly purified preparations of only rPA. These second generation rPA vaccines strive to elicit strong immune responses with substantially fewer doses than AVA while provoking less side effects. Many of the rPA candidates have shown to be effective in pre-clinical studies, but most of the second generation molecules have stability issues which reduce their efficacy over time. These stability issues are evident even under refrigerated conditions and thus emphasis has been directed to stabilizing the rPA molecule and determining an optimized final formulation. Stabilization of vaccines for long-term storage is a major challenge in the product development life cycle. The effort required to identify suitable formulations can be slow and expensive. The ideal storage for stockpiled vaccines would allow the candidate to withstand years of storage at ambient temperatures. The Fraunhofer Center for Molecular Biotechnology is developing a plant-produced rPA vaccine candidate that shows instability when stored under refrigerated conditions in a solution, as is typical for rPA vaccines. Increased stability of our plant-produced rPA vaccine candidate was achieved in a spray dried powder formulation that could eliminate the need for conventional cold chain allowing greater confidence to stockpile vaccine for civilian and military biodefense.
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, 9 Innovation Way, Newark, DE 19711, USA. Electronic address: mark.jones@fhcmb.org.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Jones
authors.affiliation: Capsugel, 64550 Research Road, Bend, OR 97701, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Burke
authors.affiliation: Capsugel, 64550 Research Road, Bend, OR 97701, USA.
authors.forename: Devon
authors.initials: D
authors.lastname: Dubose
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, 9 Innovation Way, Newark, DE 19711, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, 9 Innovation Way, Newark, DE 19711, USA.
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Manceva
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, 9 Innovation Way, Newark, DE 19711, USA.
authors.forename: April
authors.initials: A
authors.lastname: Horsey
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, 9 Innovation Way, Newark, DE 19711, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Streatfield
authors.affiliation: Capsugel, 64550 Research Road, Bend, OR 97701, USA. Electronic address: jeff.breit@Capsugel.com.
authors.forename: Jeff
authors.initials: J
authors.lastname: Breit
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, 9 Innovation Way, Newark, DE 19711, USA.
authors.forename: Vidadi
authors.initials: V
authors.lastname: Yusibov
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology; D022122:Anthrax Vaccines / Q000097:blood* / Q000276:immunology; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D007114:Immunization / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D010944:Plants / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D011208:Powders; D014614:Vaccines, Synthetic
keywords: Anthrax; Plant-produced; Protective antigen; Spray dry; Stability