On the hunt for a better vaccine.

In search of a sustainable vaccine

Text: Eva Lundgren Photo: Johan Wingborg

– I'm the first person in the entire world to do this! That thought could strike me when, as a doctoral student, I stood in the lab and conducted experiments. Just doing something new and unknown is one of the reasons why it is such fun to be a researcher.

These are the words of Davide Angeletti, Associate Professor at the Institute of Biomedicine. He has recently become a Wallenberg Academy Fellow and is working in an extremely topical area – with flu vaccines.

Davide Angeletti

Currently: Wallenberg Academy Fellow, which entails research funding for five years, with the possibility of another five years of funding. Background: Grew up in Milan, university studies at San Raffaele, Master's degree and Doctoral degree at Karolinska Institutet, Postdoctoral Fellow at the National Institute of Health, employed since 2018 at the Department of Microbiology and Immunology, Institute of Biomedicine. Family: Wife, Aishe Angeletti Sarshad, Associate Senior Lecturer at the Department of Medical Biochemistry and Cell Biology, and a six-year-old daughter Mia. Lives in: Mölndal. Hobbies: Skiing, going for walks in and around his summer cottage in Småland, cooking (Italian and Asian food), eating out, travelling, films.

he proteins found on the surface of an influenza vaccine are called haemagglutinin and neuraminidase, Davide Angeletti explains. We meet him at the Department of Microbiology and Immunology, at the top of the biomedical high-rise building on Medicinareberget, where he draws on a whiteboard in an attempt to explain. – It is haemagglutinin that is used in our flu vaccines; the body receives a small dose of the protein so that the immune system will recognize the virus strains. B-cells, a type of white blood cell, are then formed which produce antibodies and block the virus from passing on the infection.

For some reason, however, only a part of the protein, which is located at the top of the haemagglutinin, is affected. – Why that is the case, we do not know. Maybe there are simply not that many B cells further down on the haemagglutinin, or it is more difficult for the vaccine to get there. Unfortunately, it is the top of the haemagglutinin that mutates the fastest, which is why a flu vaccine does not work for very long, but must be readministered every autumn. If we could come up with a way to affect the lower parts of the virus, which are more stable and do not mutate as often, we could create a vaccine that lasts much longer. Of course, it would be even better if you just had to take a flu vaccine once to be immune for the rest of your life.

The T cells, another type of white blood cell, can also learn to recognize parts of a virus and defend the body. Perhaps it is also possible to influence the other influenza protein, neuraminidase, says Davide Angeletti. – One difficulty with researching influenza is that it is a disease that, in principle, everyone has had at some time, except small children. Studies regarding how a vaccine affects a person who has previously had the disease compared to someone who has never had it, are therefore not really possible to carry out. From a purely scientific point of view, therefore, the ongoing Covid-19 pandemic is interesting: Here we have the opportunity to investigate how different vaccines work and compare people who have had the disease with those who have not.

This is the reason for a newly started project where Davide Angeletti and his team are collaborating with teams at the Institute of Biomedicine and Sahlgrenska University Hospital, who are researching SARS-CoV-2.

– It involves trying to understand how long patients who have had Covid-19 retain their immunity. To do this, we examine blood samples from Covid patients. This provides new knowledge to us as influenza researchers while also enabling Covid researchers to avail of the much more extensive research we have on influenza.

The vaccines that are now available for Covid-19 are basically based on research on vaccines against other viruses that has been going on for several decades. Even if the research did not lead to an HIV vaccine, for example, it has nevertheless provided an enormous amount of knowledge about the immune system and led to several new technical methods. – It is really fantastic how rapidly medicine has advanced. Ten years ago, for example, it would have taken at least six months to sequence the SARS-CoV-2 virus, now it took just one month!

Perhaps all this knowledge could also be important in terms of other diseases, such as malaria, Davide Angeletti hopes. – That was the disease I studied when I was a

If we could come up with a way to affect the lower parts of the virus, which are more stable and do not mutate as often, we could create a vaccine that lasts much longer.

DAVIDE ANGELETTI

doctoral student at Karolinska Institutet. Malaria is a very serious disease where the only vaccine available does not provide more than about 30 percent protection. But perhaps all the research that is going on right now can be important there as well.

Davide Angeletti grew up in Milan where his father was self-employed, and his mother was a housewife. In upper-secondary school, he initially thought about becoming an engineer. – But then my school had a visit from a researcher, who in a very animated way told us about a laboratory discovery that eventually led to a completely new drug. That affected me deeply, so I applied to the University of San Raffaele where I took my undergraduate degree in medical and pharmaceutical biotechnology.

The fact that Davide Angeletti then completed his master's studies at Karolinska Institutet was mostly due to a coincidence.

– I had to choose between Stockholm, London, and Amsterdam, but since the educational programme at KI was more general and I thought it was too early to specialize, I applied to KI.

It was also at Karolinska Institutet that he met Aishe, whom he later married. In 2014, after completing their PhDs, they each obtained a four-year postdoctoral position at the National Institutes of Health (NIH) in Washington D.C. – Being a researcher at one of the major universities in the US is incredibly rewarding. The teams are large and dynamic, there is plenty of money and the development opportunities are fantastic. But when our daughter was born in 2015, we realized that combining family life and research was not so easy in the United States. Aishe was able to take three months paternity leave and I took one month. My mother also came to help out for a while. But when our daughter was six months old, she had to start preschool. We tried to work shifts, so that she would not have to spend too long in preschool, but it was not easy combining a job and family life.

However, it was in the United States that Davide rediscovered an interest he had had as a child. – I have always enjoyed sports and ran 100, 200 and 400 metres. As an 18-year-old, I actually came fifth in the 100 metres in the Italian Junior Championships. But I also loved skiing, something I gave up as a 16-year-old. In the US, however, I rediscovered skiing and if it had not been for the pandemic, I would be on a ski slope in Colorado right now. There you don’t have to stick to a particular piste, you can ski where you want and it is really wonderful.

In 2018, after their postdoctoral positions at NIH, Davide and Aishe got jobs at the University of Gothenburg. – Of course, Karolinska Institutet is great, but more impersonal, where each team takes care of itself. Here in Gothenburg, we are like a family, we cooperate and support each other. Furthermore, Aishe has family in Falkenberg and Borås so obviously, it’s great to be close to them.

The University of Gothenburg also provides very good support, such as from the Grants and Innovation Office, Davide Angeletti points out. – This has resulted in me receiving several grants, including two from the Swedish Research Council, and to me receiving an ERC Starting Grant in 2019. The fact that I have now become a Wallenberg Fellow entails financing for five years, with the possibility of continued financing for another five years, which means that I can invest in more risky and unexpected projects. Moreover, I will have opportunities for new collaborations, both nationally and internationally.

As an upper-secondary school student in Milan, Davide Angeletti dreamed of becoming a really great researcher who might cure cancer or do something else equally important. – Today I’m more humble. Instead, I hope to be able to make a contribution to the tremendous knowledge that all researchers around the world are working on. Even if it's just a small contribution, it's a big deal to me.