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Mannheimia haemolytica growth and leukotoxin production for vaccine manufacturing — A bioprocess review
Oppermann, Tobias; Busse, Nadine & Czermak, Peter
Abstract
Mannheimia haemolytica leukotoxin (LKT) is a known cause of bovine respiratory disease (BRD) which results in
severe economic losses in the cattle industry (up to USD 1 billion per year in the USA). Vaccines based on LKT
offer the most promising measure to contain BRD outbreaks and are already commercially available. However,
insufficient LKT yields, predominantly reflecting a lack of knowledge about the LKT expression process, remain
a significant engineering problem and further bioprocess optimization is required to increase process
efficiency. Most previous investigations have focused on LKT activity and cell growth, but neither of these
parameters defines reliable criteria for the improvement of LKT yields. In this article, we review the most
important process conditions and operational parameters (temperature, pH, substrate concentration, dissolved
oxygen level, medium composition and the presence of metabolites) from a bioprocess engineering
perspective, in order to maximize LKT yields.
Keywords
Bovine respiratory disease; Cell growth; Commensal flora of cattle; Enzootic calf pneumonia; Facultatively anaerobic; Gram-negative; Leukotoxin production; Mastitis in sheep; Operational parameters; Mannheimia haemolytica; Rod-shaped bacteria
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