title: Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.
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 10-25L 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.
authors.affiliation: Janssen Infectious Diseases and Vaccines, Archimedesweg 4, 2333CN Leiden, The Netherlands. Electronic address: bsander2@its.jnj.com.
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Sanders
authors.affiliation: Janssen Infectious Diseases and Vaccines, Archimedesweg 4, 2333CN Leiden, The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: Edo-Matas
authors.affiliation: Janssen Infectious Diseases and Vaccines, Archimedesweg 4, 2333CN Leiden, The Netherlands.
authors.forename: Natasa
authors.initials: N
authors.lastname: Papic
authors.affiliation: Janssen Infectious Diseases and Vaccines, Archimedesweg 4, 2333CN Leiden, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: Janssen Infectious Diseases and Vaccines, Archimedesweg 4, 2333CN Leiden, The Netherlands.
authors.forename: Jerome H H V
authors.initials: JHHV
authors.lastname: Custers
mesh_terms: D002460:Cell Line; D004279:DNA, Viral; D006801:Humans; D010957:Plasmids; D017955:Poliovirus; D011054:Poliovirus Vaccine, Inactivated / Q000096:biosynthesis*; D014162:Transfection; D014614:Vaccines, Synthetic / Q000096:biosynthesis
chemical_list: D004279:DNA, Viral; D011054:Poliovirus Vaccine, Inactivated; D014614:Vaccines, Synthetic
keywords: Adventitious agents; Master seed; PER.C6(®) cells; Poliovirus vaccine; Vaccine manufacturing; Vaccine safety