‘Our vaccines are still so old-fashioned!’

Flu viruses mutate so quickly that a new ‘flu shot’ needs to be developed every year. However, for one strain of the flu virus, the effectiveness of the vaccine is consistently insufficient. Robert de Vries has been awarded a prestigious ERC Starting Grant of 1.5 million euros to achieve a fundamental breakthrough in the development of vaccines for this life-threatening flu strain.

A century ago, tens of millions of people around the world died as a result of the Spanish Flu epidemic. The epidemic was caused by a strain of the flu virus Influenza A, which originated in waterfowl, but can also mutate into avian flu, swine flu, and even become potentially fatal to humans. “But now, 100 years later, we still don’t know exactly how influenza penetrates our cells. With my ERC Starting Grant, I aim to find an answer to that question, so that we can make more effective vaccines”, says De Vries..

Glycans in America

With his full beard and man-bun, Robert de Vries is easily recognisable in the corridors of the David de Wied building, where he joined the group led by Professors Roland Pieters and Geert-Jan Boons in 2014. He had crossed paths with Boons before in America, where Boons was a Professor at the University of Georgia, and De Vries was working as a postdoc at The Scripps Research Institute. Their collaboration resulted in a publication in Science about the synthesis of glycans; molecules that cover the membranes of our cells. Boons’ lab had produced glycans, and The Scripps Institute studied how certain viruses reacted to them.

There are only a few labs that can produce glycans around the world, and ours in Utrecht is one of them. So we’re in the Champions League.

Old-fashioned vaccines

Glycans act as a kind of ‘lock’ that provide viruses access to our cells. Scientists have long known that flu viruses differ in how their ‘glycan key’ fits into the ‘glycan lock’ on their victim’s cells. They had also discovered specific characteristics of the ‘glycan locks’ that allowed the virus’ ‘glycan keys’ to fit the lock. “But for Influenza A, we still don’t know what that crucial characteristic is”, exclaims De Vries. “That makes our current vaccines so old-fashioned!”

Champions League

His research has already resulted in ‘a general idea’ about what these crucial characteristics of the glycan lock for Influenza A might be. The challenge is to produce a glycan with those characteristics. Like DNA and proteins, glycans are made up of a known, but not necessarily linear, collection of building blocks. The many different branches mean that there are an enormous number of glycan variants. “There are only a few labs that can produce glycans around the world, and ours in Utrecht is one of them. So we’re in the Champions League”, jokes De Vries.

Improved vaccines

The true test of whether he is on the right track will be determined by the reactions of the Influenza A viruses to the glycans produced in the lab. To that end, the viruses are cultured in a cell under a variety of conditions. “If they then bind to the glycans, and they don’t mutate, then we will have a method for producing much better vaccines.”

Robert de Vries

Robert de Vries is an Associate Professor in the Chemical Biology and Drug Discovery group at the Utrecht Institute for Pharmaceutical Sciences. He studied Biomedical Science at the University of Amsterdam, and earned his PhD at Utrecht University under the supervision of Prof. Peter Rottier and Dr. Xander de Haan (Veterinary Medicine). He then went on to work as a postdoc at The Scripps Research Institute in the United States. De Vries’ previous grants include a LIFT subsidy for a collaborative project with FrieslandCampina (2016), a Veni subsidy (2014), and a Rubicon grant (2012).

Reserach into glycans

In 2016 Prof. Geert-Jan Boons returned from the United States to the Netherlands to take his pioneering work in the field of glycans to the next level. Watch the video about research into glycans and read more in the interview 'Geert-Jan Boons wants to turn biological problems into technological innovations'.

More information

• Science-publicatie by Geert-Jan Boons, Robert de Vries e.a.: A General Strategy for the Chemoenzymatic Synthesis of Asymmetrically Branched N-Glycans (2013)
• Publicatie in Cell Host & Microbe (2017), about how human H3N2 viruses enter cells