Supply of vital vaccines in the future without eggs

Fight against infectious diseases: vaccines without eggs

Vaccinations are a very effective remedy for various infectious diseases. For the production of vaccines, about half a billion of chicken eggs are currently needed each year. But this could change in the future. Researchers have now developed a new method that will allow some flaviviruses to be highly concentrated in bioreactors in the future.

Researchers produce pathogens in bioreactors

The production of vaccines currently requires around half a billion chicken eggs a year. For the production of flu vaccines alone, up to 500 million eggs are needed each year. However, certain vaccines could be produced without eggs in the future. Researchers at the Max Planck Institute (MPI) for Dynamics of Complex Technical Systems in Magdeburg are developing methods that allow viruses to be propagated for vaccines at a significantly higher concentration than before. The scientists produce the pathogens in cell cultures in small bioreactors.

For the production of vaccines, about half a billion of chicken eggs are currently needed each year. This could change in the future. German researchers are working on methods that allow viruses to be highly concentrated in bioreactors. (Image: arcyto / fotolia.com)

Complications and bottlenecks in the production of vaccines

According to a statement from the Institute, vaccine production often causes complications and bottlenecks.

Because manufacturing has to be planned years in advance, changing vaccination recommendations, quality deficiencies, or even economic considerations of the few companies in the vaccine market have far-reaching consequences for the supply of protective substances.

For example, the United States Center for Disease Control announced in April 2017 that the only licensed yellow fever vaccine in the United States would be out of service by the end of 2018.

As an alternative, although an agent was offered that is not licensed in the US, the limited availability of an effective vaccine in an epidemic can be dangerous.

For example, during a yellow fever epidemic in Angola and Congo in 2016, thousands of people became infected with the disease.

At that time, the World Health Organization (WHO) vaccine supply became so scarce that the helpers had to vaccinate those at risk with only one fifth of the usual dose.

Significantly higher cell concentrations

But supplying some vital vaccines could become safer in the future.

A team led by Yvonne Genzel and Alexander Nikolay from the Max Planck Institute for Dynamics of Complex Technical Systems is working to ensure that the above-mentioned problems no longer occur in the future.

The researchers are combining several approaches to produce Flaviviruses, including the Yellow Fever and Zika virus, under optimal conditions.

First, the scientists multiply animal cells in a nutrient solution-filled bioreactor, which serve as hosts for the viruses.

The cells multiply in suspension, ie floating in the nutrient solution. Connected to the bioreactor is a device that regularly aspirates and pumps back part of the solution.

A module containing dozens of nutrient-permeable membrane tubing holds the cells back, but filters spent nutrient solution and waste out of the reactor.

During this perfusion process, a probe constantly determines the concentration of the cells, to which the supply of fresh nutrient medium is adapted.

The experts in the bioreactor achieve cell concentrations that are up to 75 times higher than the usual standard.

Subsequently, the scientists infect the cells with yellow fever viruses. They use another trick to achieve the highest possible virus concentration.

The researchers use a pathogen that they have previously adapted to reproduce particularly well in animal cells.

The results of the scientists were published in the journal "Applied Microbiology and Biotechnology".

Adapt production more flexibly to the needs

"Our progress is very promising," says Yvonne Genzel, who heads a team in the Bioprocess Engineering working group at the Max Planck Institute in Magdeburg.

"The new perfusion method makes it possible to generate viruses in a small space in extremely large quantities. We achieved higher virus levels for Zika and yellow fever than any previous method could. "

Above all, perfusion methods might well be suitable for producing large quantities of viruses if the virus yield per cell is very low.

"It would be good if this technique were soon to be used by vaccine manufacturers on a large scale," explains Udo Reichl, who is the director of the Max Planck Institute for Dynamics of Complex Technical Systems and heads the bioprocess engineering group.

"The method should make it possible to adapt production more flexibly to the needs and finally to find an efficient and economical production process for viruses that are difficult to multiply."

Protection against deadly infectious diseases

Flaviviruses are usually transmitted to humans via mosquitoes and trigger infectious diseases that, like yellow fever, can be fatal.

Infection with flaviviruses can not currently be cured, medications only relieve the symptoms. However, vaccinations can protect against some of the pathogens.

Since 1937 there is a live vaccine against yellow fever, but since the first production processes were established, the production method has not changed fundamentally.

Pharmaceutical companies are still multiplying viruses in chicken embryos. From viruses without pathogenic properties, they then produce live vaccines.

On the one hand, they need eggs free of contaminants and other agents, on the other hand, the production of a vaccine takes about twelve months on this route.

Viruses for ten million vaccine doses within two weeks

In contrast, with the new production method, a bioreactor with a liter capacity will increase in just two weeks as many yellow fever viruses as are required for ten million vaccine doses.

"Unfortunately, the viruses can not be harvested directly through the hollow-fiber membrane because the membrane becomes blocked over time," says Yvonne Genzel. "That's why we're also testing other perfusion systems without a membrane."

Her team is also investigating how the perfusion methods work with other pathogens such as the flu virus, the Japanese Encephalitis virus, and the modified vaccinia Ankara virus.

The latter is a promising candidate for introducing genetic material into the cells of living beings in gene therapy.

Cancer treatment requires extremely high levels of virus to enable physicians to use this method to treat previously untreatable tumors.

If the perfusion method were to prove successful in the planned investigations, then viruses could become more readily available for many applications. (Ad)