Using electrons to inactivate viruses in vaccines

Four institutes associated with the Fraunhofer Gesellschaft in Germany have been investigating new techniques to make vaccine production more efficient

Viral inactivation by means of electron irradiation. Picture copyright of Fraunhofer IZI


Many vaccines contain viruses which need to be inactivated to prevent them from harming the recipient.

This is generally achieved by adding chemicals, but Fraunhofer scientists are taking a different approach, by using low-energy-electrons to irradiate the pathogens.

The advantages of this new method include less toxic waste, and it provides a faster and less aggressive way of rendering pathogens inactive.

Viruses in many vaccines are inactivated by means of formaldehyde. Scientists at four Fraunhofer Institutes have developed a new method that makes it easier to inactivate pathogens by using low-energy electron irradiation.

Most inoculations are based on inactivated vaccines – in other words, vaccines whose viruses have been killed and whose pathogens can no longer harm the recipient.

The individual's immune system still recognises the pathogens and produces the necessary antibodies, which provides effective protection.

However until now, chemicals – typically formaldehyde – have been used to kill the pathogens. But there are several disadvantages to this method: formaldehyde, like the other chemicals used for the same purpose, are toxic.

To minimise the risks to human health and the environment, these substances are greatly diluted when used. This means that the pathogens must be exposed to the chemical for a long time so that the pathogen is destroyed.

For example, formaldehyde takes around two weeks to inactivate the poliovirus, which triggers poliomyelitis. Any process which takes a significant amount of time is a big disadvantage for the industry.

Moreover, formaldehyde also modifies the proteins in the viruses which the immune system uses to produce the antibodies. Put another way,formaldehyde alters the viruses, which in turn reduces the effectiveness of the vaccine.

Faster pathogen inactivation

A promising alternative has been developed by researchers at the Fraunhofer Institutes for Cell Therapy and Immunology IZI, for Interfacial Engineering and Biotechnology IGB, for Organic Electronics, Electron Beam and Plasma Technology FEP, and for Manufacturing Engineering and Automation IPA.

“We use low-energy electrons to irradiate the pathogens,” says Dr Sebastian Ulbert, head of the working group at Fraunhofer IZI.

Rather than days or even weeks, a few milliseconds are all that is needed to kill off viruses or bacteria. Not only does this significantly shorten vaccine production times, the electrons destroy only the nucleic acids in the viruses and bacteria, leaving their proteins intact. The elements used to launch the desired immune response remain intact after irradiation.”

A further important benefit is that no toxic chemicals are produced.

While there have been long experiments to use irradiation to eliminate pathogens, the experimental effort required has so far proven virtually unmanageable.

For safety reasons, exposure to radioactive irradiation was only possible behind solid walls – certainly not within the production halls of the pharmaceutical industry.

“In contrast, low-energy electron irradiation is possible in a normal laboratory,” says Ulbert.

At the laboratory researchers used a scale of 10 to 15ml, and have already shown that the technique is error free: viruses are verifiably eliminated; and in initial experiments on animal models the vaccine provided comprehensive protection.

Eliminating pathogens automatically and in large numbers

In future, the scientists want to inactivate viruses in larger volumes, which is not as easy as it sounds. Low-energetic electrons penetrate less than a millimeter into the liquid containing the viruses, therefore the liquid must be presented in thin layers if the electrons are to reach every last target.

With funding from the Bill & Melinda Gates Foundation, researchers are now developing two suitable prototypes that will inactivate pathogens automatically. The first prototype is almost finished: the pre-treated solution is filled into bags, which ensures a sufficiently thin layer of liquid.

With the second prototype, researchers achieve a fine layer of liquid by running the solution over rollers. The scientists hope that clinical trials for vaccine production using these methods can start in approximately five years’ time.

However, it should be noted that the applications of this new technology is not restricted to vaccines. “Using electron irradiation, we can also inactivate hazardous material without destroying it,” says Dr. Ulbert.

The technology could be applied to blood samples taken from people infected with the Ebola virus. The blood could be prepared for safe examination in ordinary laboratories.