Stability and pre-formulation development of a plant-produced anthrax vaccine candidate

• Published in: Vaccine Vol. 35; no. 41; pp. 5463 - 5470
• Main Authors: Jones, R. Mark, Burke, Michael, Dubose, Devon, Chichester, Jessica A., Manceva, Slobodanka, Horsey, April, Streatfield, Stephen J., Breit, Jeff, Yusibov, Vidadi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 04.10.2017; Elsevier Limited
• Subjects: adverse effects; Allergy and Immunology; Ambient temperature; Animals; Anthrax; Anthrax - immunology; Anthrax Vaccines - blood; Anthrax Vaccines - immunology; Antibodies, Bacterial; Antibodies, Neutralizing - immunology; Antigens; Antigens, Bacterial - immunology; Bacillus anthracis - immunology; Bacterial Toxins - immunology; Biotechnology; Chemistry, Pharmaceutical - methods; Chromatography; cold; Drug Stability; Drug Storage - methods; Edema; Formulations; Immune response; Immunization; Immunization - methods; Life cycle engineering; Life cycle product development; Life cycles; Mice; Mice, Inbred BALB C; neutralization; neutralizing antibodies; Peptides; Plant-produced; Plants - chemistry; Powder; Powders - chemistry; Product development; Protective antigen; Proteins; Scanning electron microscopy; Side effects; Spray dry; spray drying; Stability; storage; storage time; Toxins; Vaccines; Vaccines, Synthetic - chemistry; Vaccines, Synthetic - immunology; Spray dry; Plant-produced; Protective antigen; Stability; Anthrax
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2016.12.009

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.