Novel processes to obtain pneumococcal surface proteins for vaccines.

Current pneumococcal vaccines are based on the protection offered by capsular polysaccharides from only a few from > 100 serotypes; therefore, serotype-independent vaccines composed of pneumococcal surface proteins are being developed. Despite the immense number of publications on the discovery, characterization, and evaluation of new pneumococcal vaccine candidates, there are very few that describe the bioprocess development, which is an essential step to generate material for pre-clinical and clinical tests, to obtain enough protein amount for physical-chemical, biochemical, and biological characterization, and to understand critical product and process attributes. Here, aspects of production and purification processes of pneumococcal surface proteins are reviewed, the most common bioreactor cultivation strategies are discussed, and important features of the purification process are explored to bring new insights about the correlation between protein structure and chromatography. The process development oriented to an industrial scale is an essential step for the success of novel protein-based pneumococcal vaccines and can preclude problems that could be hardly identified at flask scale production. Moreover, the early bioprocess development should favor a smooth scale-up and transfer of the process to GMP facilities for future production of new pneumococcal vaccines. KEY POINTS: • Early bioprocess development is crucial to advancing pneumococcal protein vaccines. • Bioreactor cultivation can help to identify possible process bottlenecks. • Structural features of similar proteins can orient purification process development.