Comparative study of bluetongue virus serotype 8 production on BHK-21 cells in a 50L Biostat® STR single-use bioreactors vs roller bottles

Abstract

Background Bluetongue is a major disease of ruminant livestock that can have a substantial impact on income and animal welfare. Bluetongue virus serotype 8 (BTV-8) first emerged in the European Union in 2006, peaking at 45,000 cases in 2008. Zoetis (formerly Pfizer Animal Health) licensed bluetongue vaccines (Zulvac 4 Ovis, Zulvac 1 Ovis, Zulvac 1 Bovis, Zulvac 8 Ovis and Zulvac 8 Bovis and combinations) able to prevent viremia, stressing the role of the vaccine as an aid for the epidemiological control of the disease. One important issue to be taken into account in the development of vaccines is their cost, especially in veterinary use. Vaccine production requires high-yield, stable bioproduction systems and implementation of new technologies. Mammalian cells are the substrate for production of most of the veterinary vaccines. BHK-21 cells are commonly used to produce bluetongue vaccines. As an example, the use of the BTV-8 vaccine is routinely produced in roller bottles (RB). The aim of this study is to investigate Single-Use Bioreactor technology as an alternative to RB. This technology combines the basic concept of allowing the cells to attach to a surface (microcarriers) with the advantages of suspension, which allows a better control of culture conditions and systematic and automatic culture process. Single use technology can also be an alternative to conventional production methods reducing facility complexity, possibility of the rapid expansion of the capacity of the production and to avoid the cleaning process and reduction of the risk of cross-contamination. Lower culture handling and more homogeneity can be achieved. Selection of appropriate culture conditions can be important to achieve consistent cell culture and virus production across sites and scales. Because characteristics like tank geometry and hardware (impellers, sparger) are not subject to change during scale-up, the scalability from 50L to 1000L in the BIOSTAT STR bioreactor can be an easy strategy for our production process.