title: PER.C6(®) cells as a serum-free suspension cell platform for the production of high titer poliovirus: a potential low cost of goods option for world supply of inactivated poliovirus vaccine.
abstract: There are two highly efficacious poliovirus vaccines: Sabin's live-attenuated oral polio vaccine (OPV) and Salk's inactivated polio vaccine (IPV). OPV can be made at low costs per dose and is easily administrated. However, the major drawback is the frequent reversion of the OPV vaccine strains to virulent poliovirus strains which can result in Vaccine Associated Paralytic Poliomyelitis (VAPP) in vaccinees. Furthermore, some OPV revertants with high transmissibility can circulate in the population as circulating Vaccine Derived Polioviruses (cVDPVs). IPV does not convey VAPP and cVDPVs but the high costs per dose and insufficient supply have rendered IPV an unfavorable option for low and middle-income countries. Here, we explored whether the human PER.C6(®) cell-line, which has the unique capability to grow at high density in suspension, under serum-free conditions, could be used as a platform for high yield production of poliovirus. PER.C6(®) cells supported replication of all three poliovirus serotypes with virus titers ranging from 9.4 log(10) to 11.1 log(10)TCID(50)/ml irrespective of the volume scale (10 ml in shaker flasks to 2 L in bioreactors). This production yield was 10-30 fold higher than in Vero cell cultures performed here, and even 100-fold higher than what has been reported for Vero cell cultures in literature [38]. In agreement, the D-antigen content per volume PER.C6(®)-derived poliovirus was on average 30-fold higher than Vero-derived poliovirus. Interestingly, PER.C6(®) cells produced on average 2.5-fold more D-antigen units per cell than Vero cells. Based on our findings, we are exploring PER.C6(®) as an interesting platform for large-scale production of poliovirus at low costs, potentially providing the basis for global supply of an affordable IPV.
authors.affiliation: Crucell Holland BV, Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Sanders
authors.forename: Diana
authors.initials: D
authors.lastname: Edo-Matas
authors.forename: Jerome H H V
authors.initials: JH
authors.lastname: Custers
authors.forename: Martin H
authors.initials: MH
authors.lastname: Koldijk
authors.forename: Vincent
authors.initials: V
authors.lastname: Klaren
authors.forename: Marije
authors.initials: M
authors.lastname: Turk
authors.forename: Alfred
authors.initials: A
authors.lastname: Luitjens
authors.forename: Wilfried A M
authors.initials: WA
authors.lastname: Bakker
authors.forename: Fons
authors.initials: F
authors.lastname: Uytdehaag
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.forename: John A
authors.initials: JA
authors.lastname: Lewis
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D000818:Animals; D002460:Cell Line; D016895:Culture Media, Serum-Free; D006801:Humans; D017955:Poliovirus / Q000254:growth & development*; D011054:Poliovirus Vaccine, Inactivated / Q000191:economics / Q000302:isolation & purification*; D013678:Technology, Pharmaceutical / Q000191:economics / Q000379:methods*; D019562:Viral Load; D014776:Virus Cultivation / Q000379:methods
chemical_list: D016895:Culture Media, Serum-Free; D011054:Poliovirus Vaccine, Inactivated