Synthesizing Vaccines with Microbes

Abstract

For a long time, viral or bacterial vaccines were developed by generating an attenuated or less virulent form of the pathogen with or without the combined use of chemical or physical inactivation. The emergence of approaches which enable the identification of protective components of the pathogens has led to alternative processes for manufacturing certain vaccines. In particular, advances in biotechnology allow manufacturing these components in recombinant forms by extracting them from heterologous cell production systems. Various prokaryotic or eukaryotic production systems have been explored and developed as manufacturing platforms for different vaccines. These systems can offer safer and less reactogenic products at, often times, high yields. In this chapter, examples of microbial production systems will be described. Different microbial systems which are being used to manufacture licensed vaccines are summarized. In addition, the chapter will give an outline of the potential of new technologies that are currently being tested for manufacturing of novel vaccines. We concentrate on microbial systems that are able to modify proteins with well-defined sugar structures. Pichia pastoris has been engineered to produce viral glycoproteins that are potentially more antigenic and can be produced at higher yield compared to insect or mammalian production systems. Different glycoengineered yeast cells are being used to manufacture viral glycoproteins that are currently in clinical development. A novel Escherichia coli expression system is also described that allows the glycosylation of proteins. This expression system can be used to manufacture conjugate vaccines, allowing for the first time to produce complex glycoconjugate structures in well-defined microbial production systems. Several of these conjugates that are in preclinical and clinical development are being described.