Design of Adsorptive Columns for Specific Pathogen Removal: Application to Staphylococcal Enterotoxin B

Abstract

The removal of pathogens such as toxins, viruses, bacteria, and prions in human blood, mammalian cell culture media, fermentation broths, food items, and water streams has gained increasing importance in ensuring product safety and in combatting acts of terrorism. Adsorption processes can play an important role in removing such pathogens from solution without affecting other desirable components. Adsorptive columns that can remove specific families of pathogens would need to achieve a reduction of several logs in pathogen concentration. This requirement is much more stringent than the normal yield requirements associated with adsorptive separations aimed at product recovery and purification in a process stream. This paper considers the design of an adsorptive column aimed at reducing the concentration of infectious agents from a known volume of solution by several logs in a fixed amount of time. The general rate (GR) model of chromatography is used in the analysis, including all major transport and kinetic steps in the adsorption process. The theory, with no adjustable parameters, is shown to predict with great accuracy the effect of residence time on the log removal of staphylococcal enterotoxin B (SEB) from solution using an affinity resin with a small peptide (YYWLHH) that has been found to bind specifically to this toxin.

Reversible Cyclic Peptide Libraries for the Discovery of Affinity Ligands

“…Small synthetic compounds with high affinity for biomolecules have great potential in a broad range of applications, from cell biology to medicine to protein purification. Peptides in particular are a very promising class of compounds. − Owing to their high selectivity, chemical stability, ease of synthesis, and wide structural and chemical diversity, peptides have found vast application as both diagnostic tools and therapeutics. − Many small peptides have been proposed as affinity ligands for the purification of biomolecules. − As compared to biological ligands currently used in downstream bioprocessing, these peptide-based ligands offer advantages of low cost, higher chemical stability, and lower immunogenicity. − Several linear peptides have been proposed for purification of immunoglobulins, blood factors, and therapeutic enzymes from biological fluids and cell culture. − …”