The vaccine market experienced significant growth over the last decade, with global revenues exceeding $24 billion in 2010, up from $7 billion in 2004. Major growth drivers were the increasing awareness of vaccine-preventable diseases as well as the introduction of new products. Within this growing market, glycoconjugate vaccines for the prevention of bacterial infections constitute 25% of total sales, or about $7 billion annually.
Despite the success of glycoconjugate vaccines, many challenges remain. Many pathogens important to public health lack vaccines. There have been several attempts to develop a vaccine against Staphylococcus aureus but all have failed so far. Pseudomonas aeruginosa also lacks a vaccine. Other serious pathogens missing vaccines include Neisseria meningitides group B (MEN B), the urinary tract pathogen extra-intestinal pathogenic Escherichia coli (ExPEC), and diarrheal pathogens Shigella sp., enterotoxigenic E. coli (ETEC), and Salmonella sp.
Along with the lack of vaccines, resistance development against currently available antibiotics continues to challenge public health professionals.
An important constraint on the potential for conjugate vaccines to prevent these infections is their complex chemistry-based manufacturing process (Figure 1). Manufacturing requires a multistep process of fermentation, purification, chemical processing, and cross-linking of the polysaccharide antigen with a bacterial protein carrier and a final purification step for the glycoprotein conjugate. Pathogenic organisms are required to provide the antigens, which can be challenging to manage.
The chemical conjugation process is non-specific so that there is heterogeneity in the final product and batch-to-batch variability occurs. Pharmaceutical companies have made significant strides in optimizing this process, and important vaccines are available against pathogens such as Streptococcus pneumoniae and MEN A and C. However, the chemistry-based process has not been able to tackle other important pathogens.