Stability studies for the identification of critical process parameters for a pharmaceutical production of the Orf virus |
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| Affiliation: | 1. Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen (THM), Wiesenstr.14, 35390 Giessen, Germany;2. Lab Essentials Applications Development, Sartorius Stedim Biotech GmbH, August-Spindler-Straße 11, 37079 Goettingen, Germany;3. Institute of Technical Chemistry, Leibniz University Hannover, Callinstraße 3-9, 30167 Hannover, Lower Saxony, Germany;4. Department of Immunology, University of Tuebingen, Auf der Morgenstelle 15/3.008, 72076 Tuebingen, Germany;5. Prime Vector Technologies, Herrenberger Straße 24, 72070 Tuebingen, Germany;1. Travellers’ Medical Center, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan;2. Department of Virology II, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan;3. Department of Pediatrics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan;1. Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK;2. The Vaccine Confidence Project, London, UK;3. CUNY Graduate School of Public Health and Health Policy, New York, USA;1. Department of Medicine, South Georgia Medical Center, 2501 N Patterson St., Valdosta, GA, United States;2. Pulmonary Critical Care, Albert Einstein College of Medicine, Bronx, NY, United States;3. Economics, Valdosta State University, Valdosta, GA, United States;4. Edward Via College of Osteopathic Medicine, Auburn, AL, United States;5. Philadelphia College of Osteopathic Medicine- Moultrie, GA, United States;1. China Institute of Veterinary Drug Control, Beijing, PR China;2. China Animal Husbandry Industry Co., Ltd., Beijing 100070, PR China;1. Chung-Ang University College of Nursing, Seoul, South Korea;2. Chung-Ang University Graduate School Department of Nursing, Seoul, South Korea |
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| Abstract: | A promising new vaccine platform is based on the Orf virus, a viral vector of the genus Parapoxvirus, which is currently being tested in phase I clinical trials. The application as a vaccine platform mandates a well-characterised, robust, and efficient production process. To identify critical process parameters in the production process affecting the virus’ infectivity, the Orf virus was subjected to forced degradation studies, including thermal, pH, chemical, and mechanical stress conditions. The tests indicated a robust virus infectivity within a pH range of 5–7.4 and in the presence of the tested buffering substances (TRIS, HEPES, PBS). The ionic strength up to 0.5 M had no influence on the Orf virus’ infectivity stability for NaCl and MgCl2, while NH4Cl destabilized significantly. Furthermore, short-term thermal stress of 2 d up to 37 °C and repeated freeze-thaw cycles (20 cycles) did not affect the virus’ infectivity. The addition of recombinant human serum albumin was found to reduce virus inactivation. Last, the Orf virus showed a low shear sensitivity induced by peristaltic pumps and mixing, but was sensitive to ultrasonication. The isoelectric point of the applied Orf virus genotype D1707-V was determined at pH 3.5. The broad picture of the Orf virus’ infectivity stability against environmental parameters is an important contribution for the identification of critical process parameters for the production process, and supports the development of a stable pharmaceutical formulation. The work is specifically relevant for enveloped (large DNA) viruses, like the Orf virus and like most vectored vaccine approaches. |
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| Keywords: | Downstream processing Forced degradation studies Formulation Parapox Orf virus Viral vector vaccine |
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