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Process intensification for production of Streptococcus pneumoniae whole cell vaccine
  • +6
  • Ivana Campos,
  • Celso Cardoso Jr,
  • Fernando Fratelli,
  • Muriel Herd,
  • Kristin Moffitt,
  • Ying-Jie Lu,
  • Richard Malley,
  • Luciana Leite,
  • Viviane Gonçalves
Ivana Campos
Instituto Butantan
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Celso Cardoso Jr
Instituto Butantan
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Fernando Fratelli
Instituto Butantan
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Muriel Herd
Children's Hospital Boston
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Kristin Moffitt
Children's Hospital Boston
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Ying-Jie Lu
Children's Hospital Boston
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Richard Malley
Children's Hospital Boston
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Luciana Leite
Instituto Butantan
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Viviane Gonçalves
Instituto Butantan
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Abstract

The available pneumococcal conjugate vaccines provide protection against only those serotypes that are included in the vaccine, which leads to a selective pressure and serotype replacement in the population. An alternative low-cost, safe and serotype-independent vaccine was developed based on a non-encapsulated pneumococcus strain. This study evaluates process intensification to improve biomass production and shows for the first time the use of perfusion-batch with cell recycling for a bacterial vaccine production. Batch, fed-batch and perfusion-batch were performed at 10 L scale using a complex animal component-free culture medium. Cells were harvested at the highest optical density, concentrated and washed using microfiltration or centrifugation to compare cell separation methods. Higher biomass was achieved using perfusion-batch, which removes lactate while retaining cells. The biomass produced in perfusion-batch would represent at least 4-fold greater number of doses per cultivation than in the previously described batch process. Each strategy yielded similar vaccines in terms of quality as evaluated by Western blot and animal immunization assays, indicating that, so far, perfusion-batch is the best strategy for the intensification of pneumococcal whole cell vaccine production, since it can be integrated to the cell separation process keeping the same vaccine quality.

Peer review status:ACCEPTED

03 Jan 2020Submitted to Biotechnology and Bioengineering
04 Jan 2020Assigned to Editor
04 Jan 2020Submission Checks Completed
12 Jan 2020Reviewer(s) Assigned
16 Feb 2020Review(s) Completed, Editorial Evaluation Pending
16 Feb 2020Editorial Decision: Accept