by Ivy Kupec

The work of Finnish EMBL alumnus Kai Simons proves key to Novavax approach to developing COVID-19 vaccine

Kai Simons uses a mass spectrometer to analyse lipids at Lipotype. Credit: Andre Wirsig

You could say that Kai Simons has spent a long time working on cell membranes. He started over 55 years ago in Helsinki and is still at it at 82.

His early work centred on Semliki Forest virus: an RNA virus enveloped by a membrane, which the virus acquires by budding out through the membrane of its host cell. Kai chose this virus to work on because its membrane was the simplest biological membrane in the world. It contains only one protein, the viral spike protein. The membrane, like all cell membranes, is a thin two-dimensional liquid, built from lipids (fat molecules). This simplicity was the key to success. Kai and his graduate student Ari Helenius became champions in taking the virus apart. And now, their research has played a crucial role in developing a COVID-19 vaccine currently under review by several regulatory authorities, including the US Food and Drug Administration and the European Medicines Agency.

What a Ugandan rainforest virus and SARS-CoV-2 have in common

Kai came to Heidelberg in 1975, just as EMBL was establishing itself. He brought with him two members of his group, Ari Helenius and Henrik Garoff, and together they continued their virus work. One line was to use detergents to break up the virus and produce subviral particles that could be used as vaccines. The result was protein micelles – essentially, small droplets made up of the viral spike proteins – that produced an immune response. The researchers vaccinated mice infected with Semliki Forest virus with this preparation, and found it was remarkably effective in small doses at fully protecting the mice from the virus.

This was a completely new way to make vaccines. In 1978, the group published their results in Nature, pointing out that the traditional strategy of using whole-virus vaccines – either killed or with diminished potency – was limited in both safety and effectiveness. By using only the spike proteins as a subunit vaccine, the approach of Kai and his group addressed those limitations and their research proved its effectiveness.

It was a breakthrough before its time. EMBL patented the work, but it attracted no interest in the vaccine field. The pharmaceutical industry was more interested in investing in therapeutic drugs, rather than vaccines. It has taken until now for its full potential to be realised, with US biotechnology company Novavax digging out Kai’s research to develop its COVID-19 vaccine, which they reported in a January news release had an 89% efficacy rate in a phase III clinical trial in the UK, involving 15,000 participants.

Membranes and cell biology

Later Kai got an offer to return to Finland to become the chair of the Biochemistry Department at the University of Helsinki, where he planned to shift his research fully to developing new vaccines. However, the funding of research in Finland was not optimal at the time, and when Kai was offered a permanent position by Sir John Kendrew, then Director General of EMBL, he decided to stay. He became the Coordinator of the Cell Biology Programme as part of changes to the organisation made by Sir John’s successor Lennart Philipson.

Kai’s research had taken a new direction and was now more focused on the cell biology of Semliki Forest virus infection. Ari, Henrik, and Kai found out how the virus penetrates its host cell and how its progeny escapes the cell. This work described for the first time the complete life cycle of a membrane-bound virus.

Kai then turned his attention to other aspects of cell biology, still with cell membranes as the focus. He discovered how cell membranes can compartmentalise into specialised regions, which he called lipid rafts. These are dynamic collections of specific proteins and lipids, assembling into functional hotspots where cell signalling, immune defence, and many other cellular processes take place. Kai became the father of this important organisational principle.

Beyond EMBL

In 1998, Kai left EMBL, together with three other EMBL alumni – Wieland Huttner, Tony Hyman, and Marino Zerial – to start the Max Planck Institute of Molecular Cell Biology and Genetics. Today, he is CEO of Lipotype, a biotech company he founded to analyse lipids as a service to academia and industry. Lipotype is the only company worldwide that focuses on what is termed lipidomics.

“The slogan of Lipotype is ‘lipidomics for a better life’,” Kai says. “It reflects the central role that lipids play in health and disease, as well as the hope that Lipotype technology can guide our attempts to live a healthy life.”

Kai is a steadfast supporter of increased vaccine development in all areas, not just COVID-19, noting that vaccines are superior to drugs because they can prevent bacterial, viral, and parasitic diseases. “Why not start a European vaccine institute on a scale that is capable of developing a portfolio of vaccines that could change healthcare worldwide?” he asks.

Based on notes accrued throughout his career, Kai is currently writing an autobiography, which he hopes to publish soon. He believes his time at EMBL allowed him to get involved in shaping how research should be organised and also showed him the power of multidisciplinary research.

“The most important phase at EMBL was the first phase when we learned to work together,” Kai says. “It was really quite amazing how it all started – how humble it all was. You can do much more when you work together. Truly EMBL has been more successful than we could dream of in those early days.”

This post was originally published on EMBL News