Rational Design Of Vaccines: A Long But Essential Journey

In contrast to what happened in the past, a rational approach is the best way forward – according to Professor Virgil Schijns in his inaugural speech, to be given on 14 May, on the occasion of accepting the office of ‘Professor by special appointment’ in Immune Intervention at Wageningen University.

The extremely complex defence mechanism of humans and other animals has, to a certain extent, been discovered by trial and error. In 430 BC, for example, the Greek Thucydides* described how the plague in Athens did not affect those who had recovered from it previously. Those people were therefore able to look after the sick "because they knew they would never be struck down a second time”. The first vaccinations in human beings probably took place in China and India in the seventh century when powder from pock scabs was inserted into the nose.

In Western Europe it was the English country doctor Edward Jenner who, in 1798, described a trial-and-error experiment which established him as founder of vaccinology. He took pus from a skin wound in a milkmaid who had been infected with the harmless cowpox virus and then injected it into an eight-year-old boy. After all, he already knew that milkmaids were resistant to the pox. Two months later, Jenner infected the boy with the real virus and the boy turned out to be immune – no surprise to Jenner, but he was nevertheless pleased.

An experimental approach of this kind could have ended quite differently as it did not conform to the ethically responsible route that researchers are expected to emulate these days. That is why the trial-and-error method now belongs to the past.

Rational design

The new way of exploring the potency of the immune system is to deploy rational vaccine design, Professor Schijns declared in his inaugural speech, Immune Intervention. It is a question of pressing the right buttons. "Producing vaccines in a rational way means making their functioning and safety more predictable".

The fundamental question ('the holy grail') in immunological research is how to include antigens (that invoke reactions in the body) in the vaccines in such a way that they produce the correct defence reaction by, for example, recruiting and manufacturing specialised cells that can attack the intruders.

In his function as Chair of Immune Intervention, Professor Schijns will try to discover the essential steps in and components of the biochemical reactions involved and, in addition, to deploy them for rational design of vaccines. This will not, however, mean that a preventive or therapeutic remedy has been discovered. Various hurdles have to be overcome, such as the production method, costs, the half-life (the gradual decrease in effectiveness of the drug) and an efficient way of getting the drug to exactly the right place in the body.

That is why Professor Schijns’ research group will be focusing on the cells and molecules which are still being discovered continually and which play a role in the defence mechanism. However, the group will also be focusing on known stimulants, the functioning of which is still unknown.