Empa researchers have managed to adapt a process for manufacturing certain vaccines - in particular that against Haemophilus influenzæ bacteria - for use in bioreactors, with the result that the yield is enhanced enormously.
Haemophilus influenzæ not only causes serious infection in the nose and throat, but can result in potentially fatal meningitis. The Swiss Federal Vaccination Commission threrfore strongly recommends that children be vaccinated against this organism.
So-called conjugate vaccines have proven to be especially safe and effective in this respect. In this technique, antigens in the form of sugar chains (oligosaccharides) are chemically linked to carrier proteins in a complex process known as glycosylation.
Designer bacteria instead of chemical processes
A more elegant way, however, is to allow this task to be performed by specially designed, non-toxic Escherichia coli bacteria, which are normally present in the human gut. For this purpose GlycoVaxyn has developed an enzyme-based in vivo method. The Escherichia coli bacteria were genetically modified, so that they glycosylate certain proteins - in order words, they generate vaccine material. Unfortunately, however, the yield in the GlycoVaxyn process was too low. The vaccine manufacturer needed the help of specialists to upscale their process so it could be used in bioreactors. Their search came to an end in Empa's Biomaterials laboratory, where both the necessary know-how and the bioreactors were at hand.
From cell culture to bioreactor
"This is a classic biotechnology «scale-up-problem». It is not simply a question of multiplying everything by a hundred," explains Empa expert Julian Ihssen ."On a large scale everything becomes more difficult. At higher cell densities many factors change." For example, Escherichia coli bacteria begin to produce acetic acid. The oxygen supply is also no longer optimal. This makes the results very difficult to predict.