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Supply of essential vaccines without eggs in the future

Supply of essential vaccines without eggs in the future



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Fight against infectious diseases: vaccines without eggs

Vaccinations are an extremely effective remedy for various infectious diseases. Around half a billion chicken eggs are currently needed to produce vaccines. But this could change in the future. Researchers have now developed a new method that will allow some flaviviruses to be replicated in a highly concentrated manner in bioreactors in the future.

Researchers produce pathogens in bioreactors

Around half a billion hen's eggs are currently still needed to produce vaccines. Up to 500 million eggs are used annually for the production of flu vaccines alone. However, certain vaccines could be produced without eggs in the future. Because researchers at the Max Planck Institute (MPI) for Dynamics of Complex Technical Systems in Magdeburg are developing methods with which viruses for vaccines can be replicated in a much higher concentration than before. The scientists produce the pathogens in cell cultures in small bioreactors.

Complications and bottlenecks in vaccine production

As the institute said, complications and bottlenecks often occur in the production of vaccines.

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

For example, the U.S. Center for Disease Control announced in April 2017 that the only licensed yellow fever vaccine would no longer be available in the United States by the end of 2018.

As an alternative, an agent that was not licensed in the United States was offered, but in the event of an epidemic, the limited availability of an effective vaccine can be dangerous.

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

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

Significantly higher cell concentrations

But the supply of some vital vaccines could become safer in the future.

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

The researchers are combining several approaches to produce flaviviruses, which include the yellow fever causative agent and the Zika virus, under optimal conditions.

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

The cells multiply in suspension, i.e. floating in the nutrient solution. A device is connected to the bioreactor that regularly draws in and pumps back part of the solution.

A module that contains dozens of membrane tubes that are permeable to the nutrient medium holds the cells back, but filters out used nutrient solution and waste materials from the reactor.

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

In this way, the experts in the bioreactor achieve cell concentrations that are up to 75 times higher than the usual standard.

The scientists then infect the cells with yellow fever viruses. In doing so, 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 specialist magazine "Applied Microbiology and Biotechnology".

Adapt production more flexibly to requirements

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

“The new perfusion method enables viruses to be generated in extremely large quantities in a small space. We have achieved higher virus concentrations for Zika and yellow fever than any previous method has been able to deliver. ”

Perfusion methods could be particularly well suited to producing large quantities of viruses if the virus yield per cell is very low.

"It would be good if this technology were soon to be used by vaccine manufacturers on a large scale," explains Udo Reichl, who is a director at 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 requirements and to finally find an efficient and economical production process for viruses that are difficult to reproduce."

Protection against fatal infectious diseases

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

Infection with flaviviruses cannot currently be cured, medication only alleviates the symptoms. However, vaccinations can protect against some of the pathogens.

A live vaccine against yellow fever has been around since 1937, but the production method has not changed fundamentally since the first production processes were established.

Pharmaceutical companies are still multiplying the viruses in chicken embryos. They then produce live vaccines from viruses with no disease-causing properties.

On the one hand, they need eggs that are not contaminated by foreign substances and other pathogens, on the other hand, the production of a vaccine in this way takes about twelve months.

Viruses for ten million doses of vaccine within two weeks

With the new production method, however, in a bioreactor with a capacity of one liter, as many yellow fever viruses as are needed for ten million vaccine doses are needed in just two weeks.

"Unfortunately, the viruses cannot be harvested directly through the hollow fiber membrane because the membrane clogs over time," says Yvonne Genzel. "That is why we are 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.

In cancer treatment, extremely high virus concentrations are required so that doctors can use this method to treat previously incurable tumors.

If the perfusion method were to prove itself in the planned studies, viruses could therefore become more readily available for many applications. (ad)

Author and source information


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