Investigation and Application Progress of Vero Cell Serum-free Culture

Abstract

Serum-free culture is now becoming the general trend of biological production. Its application in Vero cell culture is significant. In the present paper, we reviewed factors affecting Vero cell serum-free culture and several culture techniques. In light of these reviews, we outlined its extensive application prospect. 1. Background of Vero cell serum-free culture Vero cells are considered as a substrate for the production of viral vaccines. Vero cells were first separated from a normal adult African green monkey kidney cell line by Yasumura of Chiba University, Japan in 1962. This cell line presents several advantages over primary and diploid cell substrates. Vero cells are easily available, grow fast and ķ require no rigor culture conditions which can support various virus proliferations; Vero cells have been extensively ĸ characterized to evaluate their oncogenic potential. Several studies have shown that this cell line is free from oncogenic property and is not presenting any threat to human health when used as a substrate for biological production authorized by the World Health Organization (WHO); Vero cells can be used in microcarrier and suspension cultures for large Ĺ scale production in bioreactors. Moreover, virus titer achieved is higher than that reached using other types of cell substrates. These properties greatly facilitate the transfer of vaccine-producing capability to developing countries, which is an important goal of WHO. Cell cultures have been used extensively in the manufacture of biologicals for diagnostics, therapeutics and vaccines. The production of vaccines by animal cell culture was one of the earliest commercial applications of in vitro animal cell technology, and despite the recent spotlight accorded recombinant protein products, vaccines remain the most significant application of cell culture in terms of product numbers and social impact. Product safety is of paramount concern since the majority of viral vaccines are for use in healthy paediatrics. Cell substrate, production cultures, culture conditions, production media, detachment agents, etc. are major issues of safety considerations (Rourou, 2007). One of the important points of safety concerns relates to the composition of culture medium. All classical vaccine production processes make use of animal derived substances: serum, trypsin, lactalbumin, etc. Animal sera are required for vigorous growth of animal cells used as substrate for virus propagation. Serum was shown to have several essential functions in culture. It is a source of nutrients, hormones, growth factors and protease inhibitors. Furthermore, serum facilitates the attachment and spreading of cells, and provides nonspecific protection against mechanical damage and shear forces. In addition, it is able to bind to toxic compounds. However, besides these growth-promoting properties, serum has some major disadvantages. It is undefined with respect to its chemical composition. It can be a source of adventitious agents and their by-products. Serum also presents a variable performance of cell growth and has a substantial cost. Therefore, the benefits of in vitro culture of animal cell lines in the absence of serum are widely acknowledged. The removal of serum components and the elimination of other animal-derived raw materials are proving more challenging. Processes for serum free culture of several cell types expressing r-DNA derived proteins and monoclonal antibodies (MAbs) have been developed and established for large scale production since the beginning of the 1990s. However, the picture is different for existing conventional biotechnology products such as viral vaccines, the scientific challenge is probably greater because diploid cell lines or even continuous cell lines (CCLs) such as Vero cells may require additional growth and attachment factors that CCLs growing in suspension culture do not need. Serum free culture applied in production area would give greater application potential and broad market prospect Vero cells. Serum free culture of Vero cells has been an important focus on produce and research currently or for the future.