Bilotkach K. Industrial technology development for cultivation biological agents in production rotaviral antigens

The dissertation develops technology for industrial cultivation of anchorage-dependent embryonic porcine kidney cell culture (ADCC EPK) and ape rotavirus SA-11. The products of cultivation are used for production of anti-rotavirus vaccine. Materials, commercially available in Ukraine, are tested as potential carriers for cultivation of anchorage-dependent animal cell cultures to be used in fixed-bed cultivation systems. Optimization of conditions and regimes for cultivation and inoculation of biological agents is also studied. Results show that cultivation of anchorage-dependent cell cultures (ADCC) is possible on polymers, which are easily commercially available in Ukraine, such as low density polyethylene film for use in agriculture and food industry. A new cultivation medium recirculation and aeration system is offered; the system is located inside the bioreactor and uses the Archimedes water lifting mechanism. Semi-continuous ADCC EPK cultivation regime is developed, with concentrated growth substrates introduced in batches. The volume of growth substrates and dilution factor of cultivation medium are determined using the special algorithm, supporting optimal ADCC EPK cultivation regime. Implementation of the proposed ape SA-11 rotavirus vaccine cultivation technology, as well as of substrate for its reproduction - anchorage-dependent embryonic porcine kidney cell culture (ADCC EPK) allowed increasing output of infectious active virus by 2.0 lg TCD50. Output of antigen titer has been increased 4 times as compared to classical cultivation technology of biological agents under consideration.