Use of conjugate vaccines for combating infectious diseases in the developing world is currently limited by production costs. Production in recombinant Escherichia coli (E coli) is potentially a simpler, more cost-effective method that would make vaccination campaigns economically viable.
Writing in the journal Microbial Cell Factories researchers describe producing potential vaccines against shigellosis, a disease responsible for 1m deaths a year in the developing world, using recombinant E coli.
Glycosylation of carrier proteins occurred in E coli cultivated in 2.5L or 3.5L fed-batch bioreactors. Using this process the researchers produced bioconjugates that are potential vaccines against shigellosis.
“In this work it was demonstrated for the first time that glycosylated proteins can be produced in recombinant E coli at a larger scale in fed-batch culture”, wrote the researchers. However, time-space-yields for glycoconjugates are still low compared to methods using recombinant proteins.
Increasing yields
Despite this current shortcoming the researchers believe the technique has potential. Amounts of glycoconjugate needed per vaccination are relatively low and applying different methods could increase yields.
For instance, the researchers suggest process modifications could result in more complete glycosylation of carrier proteins. Alternative strains of E coli hosts could also increase yields, as could optimisation of the sequence context of glycosylation sites in carrier proteins.
Identification of metabolic bottlenecks and subsequent molecular engineering of host strains is also on option. Finally, protein engineering could be used to improve functional expression or catalytic efficiency.
Successfully increasing the yield could make in vivo production a viable alternative to the multi-step process which is currently used to manufacture conjugate vaccines.