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Thomas Michiels

There are a number of vaccines that require animal testing in their production. Thomas Michiels developed a replacement lab test that allows manufacturers to achieve the same result, without involving animals. The next step is that the test has to be validated by pharmaceutical companies and has to be further evaluated by regulatory bodies.

Corona vaccines are in the spotlight at the moment, but other vaccination programmes are also ongoing, for example against diphtheria and tetanus, through the DTP injection that children receive. These are among the oldest vaccines we use, and they work efficiently. But there is still room for improvement, according to Michiels. The point is that diphtheria and tetanus vaccines are made using bacterial toxins, proteins that are quite toxic in their natural form. That's why they are chemically inactivated, but after such a treatment, experiments are necessary to determine whether the toxin has indeed been rendered harmless, while at the same time offering protection against infection with the bacteria. For each batch of vaccines, new animal experiments are needed to determine whether the ingredient is safe and effective.

Smarter alternative

This approach has been the standard quality control for the past hundred years, and according to Michiels it is time to develop a smarter alternative. ‘The idea is to phase out these animal tests,’ says Michiels. ‘To do that, we need a simple laboratory test that shows that a vaccine factory makes a consistent product that is identical week after week. You want a simple test that can do the job. Manufacturers also want that, because animal tests sometimes produce variable results, are expensive and have ethical concerns.’ 

Test tube

Michiels’ PhD research sought the solution in mimicking a small part of the immune system. Our immune cells absorb toxin protein and cut it into small pieces, after which the actual immune reaction begins. Michiels took one enzyme from immune cells, and let it digest the toxin in a test tube. The resulting fragments are measured in a sensitive analysis device. ‘The results of that measurement – the rate of degradation – can be linked to the quality of the vaccine. A bad batch of toxin, for example, is broken down too quickly and produces a deviating result in the test.’

‘The idea is to phase out animal tests.’

From proof of principle to prototype

The next step in this project is that each vaccine manufacturer applies the lab test in their own quality control, and that government agencies approve this new approach. All these parties were already involved in the supervision of his project, so the will to bring the introduction of the lab test to a successful conclusion is definitely there, says Michiels. All in all, in four years his research has reached its goal, from proof of principle to a prototype test. ‘It became clear pretty quickly that the concept was right. I think the final goal has been achieved by paying attention to the balance between scientific insight and technological simplicity, so that labs will be able to apply it in the future.’


In high school, Thomas Michiels (1991) had doubts about becoming a pharmacist. He found medicines very interesting, but wanted to focus on how to develop and improve them. He therefore chose to study Bio-Pharmaceutical Sciences in Leiden. His PhD research took place at the LACDR, while he was seconded to Intravacc in Bilthoven, the company that emerged from RIVM's vaccine research. Michiels currently works at Intravacc as a researcher.  

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