How to choose the correct cell line for producing your viral vaccine: what is important?

Abstract

Background Human viral vaccine manufacturing formed the basis of using animal cell technology for biopharmaceuticals in the 1960–1970s, replacing products derived from animals or human blood [1]. The majority of recombinant protein products, such as hormones and blood factors, made this transition from mammalian to a recombinant source, and later, being relatively well-characterized products, adopted stringent regulatory guidelines [2] based on scientific understanding. This also led to the use of a limited number of standard target expression systems to generate a product with specific predefined product characteristics and quality (CHO, Escherichia coli, Saccharomyces or Picchia). In contrast to recombinant biopharmaceutical proteins, the present situation for viral vaccines is characterized by a lack of standardization and diversity in expression systems. This diversity is further enhanced by the various approaches followed in viral vaccine development. Although recombinant subunit products to generate viral vaccines, such as virus-like particles (hepatitis B and human papillomavirus) and virosomes (Inflexal V; Crucell, The Netherlands), have reached the market, the majority of viral vaccines, as discussed in this paper, still takes the production of viruses (split, inactivated or live attenuated) as a starting point. Since most vaccines are given to healthy children, the introduction of new cell lines in viral vaccine production has been a low priority compared with product safety. Therefore, manufacturers may have selected cell lines based on conservative approaches, while tolerating potential inefficiencies. However, recent endeavors in modernization of classical (e.g., influenza and polio) and new (e.g., respiratory syncytial virus) viral vaccines have initiated exploration of exciting new viral expression systems [3].