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Sabin-IPV (or sIPV, inactivated polio vaccine based on attenuated Sabin strains) is anticipated to replace the oral polio vaccine for the endgame in polio eradication. Optimization of sIPV production will lead to a better economically feasible vaccine. To assist process optimization, we studied Sabin type 1 poliovirus (PV) infection kinetics on Vero cells in controlled bioreactor vessels. The aim of our study was to develop a descriptive mathematical model able to capture the dynamics of adherent Vero cell growth and PV infection kinetics in animal component free medium. The model predicts the cell density, metabolites profiles, and viral yields in time. We found that the multiplicity of infection (MOI) and the time of infection (TOI) within the investigated range did not affect maximal PV yields, but they did affect the process time. The latter may be reduced by selecting a low TOI and a high MOI. Additionally, we present a correlation between viral titers and D-antigen, a measure for immunogenicity, of Sabin type 1 PV. The developed model is adequate for further studies of the cell metabolism and infection kinetics and may be used to identify control strategies to increase viral productivity. Increased viral yields reduce costs of polio vaccines with large implications on public health.

Worldwide efforts to eradicate polio caused a tipping point in polio vaccination strategies. A switch from the oral polio vaccine, which can cause circulating and virulent vaccine derived polioviruses, to inactivated polio vaccines (IPV) is scheduled. Moreover, a manufacturing process, using attenuated virus strains instead of wild-type polioviruses, is demanded to enhance worldwide production of IPV, especially in low- and middle income countries. Therefore, development of an IPV from attenuated (Sabin) poliovirus strains (sIPV) was pursued. Starting from the current IPV production process based on wild type Salk strains, adaptations, such as lower virus cultivation temperature, were implemented. sIPV was produced at industrial scale followed by formulation of both plain and aluminium adjuvanted sIPV. The final products met the quality criteria, were immunogenic in rats, showed no toxicity in rabbits and could be released for testing in the clinic. Concluding, sIPV was developed to manufacturing scale. The technology can be transferred worldwide to support post polio-eradication biosafety goals.

HighlightsVero cells were grown in batch, semi-batch, perfusion and recirculation strategies.At high cell densities (to 5 × 106 cells mL−1) cells were infected with poliovirus.Increased cell densities allowed 3 fold increase in d-antigen yield.Cell specific d-antigen yields were lower at higher cell densities.The semi-batch cultivation strategy is most promising for optimization.