| Autor: |
Gerritzen MJH; Institute for Translational Vaccinology (Intravacc), Process Development Bacterial Vaccines, P.O. Box 450, 3720, AL, Bilthoven, The Netherlands.; Bioprocess Engineering, Wageningen University, P.O. Box 16, 6700, AA, Wageningen, The Netherlands., Stangowez L; Institute for Translational Vaccinology (Intravacc), Process Development Bacterial Vaccines, P.O. Box 450, 3720, AL, Bilthoven, The Netherlands., van de Waterbeemd B; Institute for Translational Vaccinology (Intravacc), Process Development Bacterial Vaccines, P.O. Box 450, 3720, AL, Bilthoven, The Netherlands.; Dept. Drug Substance Development, Janssen Vaccines and Prevention, Archimedesweg 4-6, 2333, CN, Leiden, The Netherlands., Martens DE; Bioprocess Engineering, Wageningen University, P.O. Box 16, 6700, AA, Wageningen, The Netherlands., Wijffels RH; Bioprocess Engineering, Wageningen University, P.O. Box 16, 6700, AA, Wageningen, The Netherlands.; Faculty of Biosciences and Aquaculture, Nord University, P.O. Box 1409, 8049, Bodø, Norway., Stork M; Institute for Translational Vaccinology (Intravacc), Process Development Bacterial Vaccines, P.O. Box 450, 3720, AL, Bilthoven, The Netherlands. michiel.stork@intravacc.nl. |
| Abstrakt: |
Outer membrane vesicles (OMVs) are nanoparticles secreted by Gram-negative bacteria that can be used for diverse biotechnological applications. Interesting applications have been developed, where OMVs are the basis of drug delivery, enzyme carriers, adjuvants, and vaccines. Historically, OMV research has mainly focused on vaccines. Therefore, current OMV production processes have been based on batch processes. The production of OMVs in batch mode is characterized by relatively low yields and high costs. Transition of OMV production processes from batch to continuous processes could increase the volumetric productivity, reduce the production and capital costs, and result in a higher quality product. Here, we study the continuous production of Neisseria meningitidis OMVs to improve volumetric productivity. Continuous cultivation of N. meningitidis resulted in a steady state with similar high OMV concentrations as are reached in current batch processes. The steady state was reproducible and could be maintained for at least 600 h. The volumetric productivity of a continuous culture reached 4.0 × 10 14 OMVs per liter culture per day, based on a dilution rate of 1/day. The tested characteristics of the OMVs did not change during the experiments showing feasibility of a continuous production process for the production of OMVs for any application. |
