The Use of Serum Albumin to Increase Viral Yield during Vaccine Production
In the production of vaccines, it is a goal to achieve as much viral yield as possible. Increasing the yield of the virus lowers the overall cost of the vaccine. The lower cost, in turn, improves distribution of the vaccine, particularly in the developing world where high vaccine cost is a barrier for widespread vaccinations. During the production of a vaccine, cells are typically seeded into culture and infected with virus a couple days later. The virus is collected a few days after infection. Thus, the process consists of two phases: a cell growth phase prior to viral infection and a production (maintenance) phase where cells must support the production of virus. During both phases serum is often used to promote cell growth and productivity, but the use of serum in vaccine production creates problems. Serum is inhibitory to the production of some viruses such as influenza. More importantly, bovine serum components are often carried into the vaccine as a contaminant from the cell culture medium. Furthermore, the recent discovery of bovine spongiform encephalopathy (BSE) is likely to limit the continued use of bovine serum and other animal derived components in culture processes for vaccines. Thus, a problem exists during vaccine production. — What is the best keep method to keep cells healthy in order to maximize viral yield without introducing bovine based contaminants or infectious agents?
Publications have shown that viral yield can be increased in some viral systems by the use of serum albumin as a medium supplement. Gitnick et al (1) found that serum-albumin can effectively replace bovine serum in post-infection medium for the production of rubella virus. Albumin also increased the titer of virus compared to without FBS supplementation. Today, albumin continues to be used in the production of the rubella component of the MMR vaccine (2). Albumin also increases the yield of viruses such as rabies (3, 4) and others (5). Albumin while better than serum, still doesn’t address the problem of animal or human contamination. As a result, the best approach is to utilize an albumin that is able to support the health of cells in addition to being regulatory friendly – such as animal-free recombinant human albumin.
1. Gitnik, G.L et al. (1968) Appl. Microbiol. 16, 430-432.
3. Kallel, H et al. (2003) Appl. Micro. Biotechnol. 61, 441-446.
5. Schiff, L, and Shefner, A (1975) J. Clin. Microbiol. 1, 44-59.