Stability studies for the identification of critical process parameters for a pharmaceutical production of the Orf virus

verfasst von

Friederike Eilts, Jennifer J. Labisch, Sabri Orbay, Yasmina M.J. Harsy, Marleen Steger, Felix Pagallies, Ralf Amann, Karl Pflanz, Michael W. Wolff

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.

Organisationseinheit(en)

Institut für Technische Chemie

Externe Organisation(en)

Technische Hochschule Mittelhessen
Sartorius AG
Eberhard Karls Universität Tübingen
Prime Vector Technologies GmbH

Typ

Artikel

Journal

Vaccine

Band

41

Seiten

4731-4742

Anzahl der Seiten

12

ISSN

0264-410X

Publikationsdatum

19.07.2023

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Molekularmedizin, Allgemeine Immunologie und Mikrobiologie, Allgemeine Veterinärmedizin, Öffentliche Gesundheit, Umwelt- und Arbeitsmedizin, Infektionskrankheiten

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1016/j.vaccine.2023.06.047 (Zugang: Geschlossen)