Interview with dr Alicja Chmielewska from the Department of Molecular Biology of the Interuniversity Faculty of Biotechnology UG and GUMed

Research on COVID-19 has pushed all else into the background. Is this an unprecedented situation or have we already encountered research conducted on such an intensive and large scale?

We can point to moments in the history of science when very intensive research was carried out.  This was the case, for example, at the time when the HIV virus appeared. However, given the severity of the SARS-CoV-2 threat, the scale of the research and its advancement, the current situation is unprecedented. Technological and biotechnological advances have meant that we are getting some solutions much faster. It took a very long time for scientists to isolate the HIV virus and establish that it belongs to the retrovirus family. In the case of the current pandemic, it was possible to obtain the genetic sequence of the SARS-CoV-2 virus at breakneck speed, and this information has given scientists all over the world the first tools for further work. Knowing the sequence alone is enough to produce viral proteins in different systems and see if they will be good 'candidates' for a vaccine. Previously, we had to work with infectious material, but thanks to developments in genetic engineering, we no longer have to work with an infectious virus to learn something about it.

The term 'genetic engineering' sounds threatening. Can we 'disenchant' it?

Genetic engineering is cutting and joining together pieces of nucleic acid sequences to obtain new properties for encoded proteins. Nucleic acids are natural parts of our cells. They include DNA, in which our genes are written, and RNA which acts as an information transmitter. Thanks to genetic engineering, we can freely design fragments of nucleic acids so that they code for different proteins, such as vaccine proteins. Such vaccine proteins can be produced in in vitro cell cultures, i.e. cultures grown in laboratory vessels.

You have been among the beneficiaries of programmes that have provided additional funds for coronavirus research. What are you working on now?

I obtained funds for research on COVID-19 from the Polish Science Foundation. It is a small grant for a one-year extension of my project, which concerned mechanisms of cell defence against viruses and possibilities of using these mechanisms as therapeutic strategies. Part of this grant is to introduce the so-called model system to study the SARS-CoV-2 virus. In studies on dangerous viruses more secure models are often used, which allow for working in laboratories with less security. For the time being, we cannot yet work at the University of Gdańsk with the so-called live virus due to the lack of a laboratory with the appropriate level of security. The model we are working with is pseudo particles of the SARS-CoV-2 virus. These are particles coated with surface proteins of the SARS-CoV-2 virus, which are used by the virus to enter our organism in the manner of a so-called 'lock key'. The 'locks' are on our cells, the cell receptors, and the viruses have the 'keys' they need to enter these cells. Such a system is suitable for testing the initial stage of a viral infection. We are using it to see if certain compounds can block the 'key' from binding to the 'lock' and thus inhibit the virus from entering the cell. We cooperate with several different research units in Poland and abroad, checking, among other things, whether the compounds obtained by scientists inhibit the penetration of the virus into cells. 

The University of Gdańsk received a PLN 4 million targeted grant for the adaptation of the existing laboratory at the Institute of Biotechnology and upgrading it to a BSL-3+ class. Will this allow for this kind of research?

Of course! We are very happy about it and we are all waiting for it. It is important to note that the model system we can currently work with is somewhat artificial and is the first stage of research. We can see how the virus binds to the cell and how it is then transported into the cell, but we do not know what happens afterwards, such as how the genome is replicated or how progeny viruses are released from cells. For this, we need tests on infectious material.

In general, biotechnology in Gdańsk, including research at the University of Gdańsk in the SARS-CoV-2 area, is at a very high, world-class level.

This is mainly thanks to our masters, in my case Professor Krystyna Bieńkowska-Szewczyk. Excellent work has been done, for example, by dr Łukasz Rąbalski with his rapid sequencing of the virus, as well as by other colleagues from my department and other departments of the Intercollegiate Faculty of Biotechnology UG and GUM-ed. We try to be open-minded, collaborate with different research centres and take advantage of the latest technological opportunities.

To what extent does the social responsibility of science and sharing research results work in the field of SARS-CoV-2 research, and to what extent does patent protection prevail?

When it comes to coronavirus research, it was unique from the beginning that all scientific articles on the subject were published in open access. Everyone could read them. This was decided by the publishers of the scientific journals themselves, where access to the latest research had hitherto been paid for. Some scientists also chose to publish their research results on various portals before their publications went through the review stage. These publications should of course be approached with caution as they are not peer-reviewed, but they do give you an idea of whether someone is doing similar research to yours and whether you might be able to work with them. Scientists are widely sharing their research on SARS-CoV-2, but I do not know what this looks like at the level of large companies and their development of preparations or vaccines that are commercially sold. There are completely different mechanisms at play here.

To what extent is a COVID-19 vaccine, which is genetic, likely to revolutionise the way vaccines are developed against other diseases?

Research on genetic vaccines was already being done before the pandemic. Genetic vaccines were being tested against HIV and HCV, and vaccines based on RNA particles were being tried for introduction when the Zika virus epidemic occurred. Fortunately, that outbreak died out quickly, but as a result, there was no more vaccine testing or funding to continue research. During the COVID-19 pandemic, previously developed technological platforms were used. Enormous resources and a very large number of scientists were deployed to conduct a huge number of clinical trials and to launch the finished product. The work of these research teams has been successful. We are vaccinated with genetic vaccines. It is always the most difficult to get a process off the ground. This stage is behind us. We can now improve genetic vaccine research and the processes involved. Each subsequent vaccine has the potential to be developed more quickly, more efficiently and more effectively. This revolution is happening here and now.

However, to cool down the enthusiasm and the very high expectations that have been aroused, it is worth remembering that these are not vaccines for all types of viruses. All the diseases that plague humanity will not disappear...

Of course. Fortunately, it turned out that a fairly simple vaccine works against the SARS-CoV-2 virus. In fact, we transfer genetic material containing a surface protein, so a vaccine based on the so-called spike protein worked. When I was preparing my dissertation, I was interning for two years at a company that develops genetic vaccines and conducts pre-clinical and clinical trials. At that time, we were developing a genetic vaccine against hepatitis C. I prepared several versions of a vaccine very similar in the mechanism of action to that of Oxford against COVID-19. The vaccine we developed induced an immune response in animals and the formation of antibodies in them. But for HCV this is unfortunately not sufficient. Attempts to develop genetic vaccines for HIV have also been unsuccessful, as the virus builds its genetic material into our cells and remains there. A great deal, therefore, depends on the biology of the pathogen itself.

Is there any way to dispel all the myths about COVID-19 vaccines?

There are so many that it is very difficult, but as scientists, we cannot give up. We spend a lot of time trying to convince people that vaccines are safe and effective. However, to dispel even the most dangerous myths, much more time is needed...

Therefore, we will return to harmful myths in the next article. In conclusion, however, let us try to assure you that vaccines against COVID-19 are safe and it is worth getting vaccinated.

As I said earlier, genetic vaccine research had been carried out much earlier, and it was only strongly intensified during the pandemic period thanks to a lot of money and the involvement of a huge number of scientists. All the COVID-19 vaccines were tested in very large clinical trials. These trials have proven that they are safe and effective. We, therefore, have to weigh up the very hypothetical probability of side effects, which we cannot rule out completely, against a dangerous virus that kills here and now, not hypothetically at all. Common sense should always prevail. Let us trust the scientists.

Thank you for the interview.

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dr Alicja Chmielewska - assistant professor in the Department of Molecular Biology of Viruses Interuniversity Faculty of Biotechnology of the University of Gdańsk and Gdańsk Medical University.

During her PhD studies, she had a two-year internship in the laboratory of the CEINGE institute in Italy, in collaboration with the biotechnology company Okairos. She participated in studies on an experimental genetic vaccine against the hepatitis C virus, constructed and tested vaccines based on adenoviral vectors. She continued her work on genetic vaccines in the Department of Molecular Biology of Viruses. Currently, she directs research on the action of cellular antiviral proteins, including their role in SARS-CoV-2 infection. She is involved in dissemination of science and cooperates with publishers for the medical community.