Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6® cell based inactivated poliovirus vaccine. Issue 42 (13th October 2015)

• Record Type: Journal Article
• Authors: Sanders, Barbara P.; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H.H.V.
• Is Part Of: Vaccine. Volume 33:Issue 42(2015)
• Page Start: 5498
• Page End: 5502
• Publication Date: 2015-10-13
• Subjects: IPV inactivated poliovirus vaccine -- OPV oral poliovirus vaccine -- MVS Master Virus Seed -- PV poliovirus -- TCID50 Tissue Culture Infectious Dose 50%; Poliovirus vaccine -- Master seed -- Vaccine manufacturing -- PER.C6® cells -- Vaccine safety -- Adventitious agents; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.08.081
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Synthetic vaccine seeds were derived encoding wild-type poliovirus genomes. Synthetic polioviruses were phenotypically and genetically identical to wild-type polioviruses. Synthetic polioviruses were genetically stable and show high yields in PER.C6 ® cells. Synthetic vaccine seeds allow a fully documented and traceable passage history. Synthetic seeds augment vaccine safety by reducing risks of contamination by adventitious agents. Abstract: Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10–25 L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 ® cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 ® cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents.