Plasma-derived human serum albumin (pHSA) or bovine serum albumin are commonly added to cell culture media used in cell culture-based vaccine and therapeutic production, because it enhances cell growth and increases protein productivity. However, the use of pHSA carries the risk of transmission of virus and emerging infectious pathogens, such as prions, from blood for which no tests are available. In addition, existing heat treatments for blood and blood products are ineffective for prions and possibly unidentified infectious agents. Because millions of people are immunized annually with cell culture-based vaccines and millions more require cell culture-based therapeutics for the treatment of various disorders, regulatory agencies have called for the replacement of pHSA in vaccine and therapeutic production with recombinant HSA (rHSA). In this Phase I proposal, the goal is to test the effectiveness of rice-derived rHSA compared to pHSA as an ingredient in cell culture media. Growth studies will be performed on Vero, hybridoma AE1, and Chinese hamster ovary (CHO) cells cultured in serum- free cell culture media supplemented with rHSA. Determination of cell mass, growth rate, and viability on all three cell lines will be measured. In addition, monoclonal antibody production by AE1 and CHO cells will be quantitatively measured using IgG-specific enzyme linked immunosorbent assays. The similarity of growth, development, and protein productivity of cells cultured in rHSA supplemented cell culture media to pHSA supplemented media will lead us to scale-up in Phase II, which will be to determine the growth of cells in the presence of rHSA in bioreactors and assess the ability of cells to produce vaccines. If successful, our project will have addressed the call by agencies for a safe alternative to pHSA and animal blood products in vaccine and therapeutic production. Safety concerns regarding human-to-human transmission of emerging infectious pathogens from the use of plasma-derived human serum albumin (pHSA) and blood products as an ingredient in cell culture media for cell-based vaccine and therapeutic production exist. Regulatory agencies have called for the replacement of pHSA with recombinant HSA. In response, an inexpensive source of recombinant HSA produced in rice would not only assure a safe alternative to pHSA, but would also allow cost- effective production of cell-based vaccine and therapeutics. ? ? ?
