Infection with the Hepatitis B virus (HBV) continues to represent a significant problem worldwide: over two billion people are infected and 350 million suffer from chronic Hepatitis B. One of the countries in which Hepatitis B frequently occurs is India. In a German-Indian collaboration researchers from the Braunschweig Helmholtz Centre for Infection Research (HZI) have now developed a new method that enables large quantities of Hepatitis B vaccine to be generated at particularly low cost. The findings have been published in the free online scientific journal Microbial Cell Factories. The information is accessible to all and is not subject to patent. "We have published this information in an open access journal and waived patents, thus making it freely accessible to all," says Ursula Rinas of HZI, who heads the German team involved in the project.
Until the beginning of the 1980s researchers isolated empty, uninfected viral envelopes from the blood of patients suffering from Hepatitis B, with these subsequently processed to form a vaccine. It soon became apparent that the provision of one component of the viral envelope was sufficient for a successful vaccination. Following this, the component was produced artificially in laboratories using the familiar baking yeast Saccharomyces cerevisiae, where it was then isolated on a large scale. The Hepatitis B vaccine was consequently the world's first recombinantly-produced vaccine.
For many people in poorer countries medicines are too expensive. The use of the recombinant Hepatitis B vaccine is not possible in these countries due to the costs involved. A further problem is patents that prevent medicines from being copied and marketed cheaply for decades. It is only when these patents lapse that these so-called generic medicines can be manufactured cheaply.
The German-Indian collaboration aimed to develop a new Hepatitis B vaccine that could also be accessible to people in poorer countries. The researchers attempted to raise the yield of virus particles with the aid of another producer and subsequently reduce the costs. They turned to the yeast fungus Pichia pastoris, modifying the fungus in such a way that, growing on a specific medium, it produces the component of the viral envelope. The result was a pleasing one for the researchers: "With one litre of yeast culture we can produce around 300,000 vaccination doses for children. This is the highest-known yield for this vaccine to date and around seven times as much as was previously known," says Rinas.
In future the researchers aim to use the same system to produce a vaccine for Dengue fever.
Original article: Simple high-cell density fed-batch technique for high-level recombinant protein production with Pichia pastoris: Application to intracellular production of Hepatitis B surface antigen. Chandrasekhar Gurramkonda, Ahmad Adnan, Thomas Gabel, Heinrich Lunsdorf, Anton Ross, Satish Kumar Nemani, Sathyamangalam Swaminathan, Navin Khanna and Ursula Rinas. Microbial Cell Factories 2009, 8:13 (10 Feb 2009)
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