Results of the preclinical testing of the Covid-19 vaccine
Ljubljana, 31 August 2020- At the National Institute of Chemistry, we prepared a press conference to present the results of the preclinical development and testing of the Covid-19 vaccine. The results were presented by Prof. Dr. Roman Jerala, head of the research team developing the vaccine. Participating in the press conference were also Director of the National Institute of Chemistry, Prof. Dr. Gregor Anderluh, who gave an account of the efforts devoted by the Institute to fighting this dangerous disease, and Prof. Dr. Borut Štrukelj from the Faculty of Pharmacy at the University of Ljubljana, who commented on the results achieved.
With more than 25 million infected so far and a death toll closing on one million, the Covid-19 pandemic has led to devastating consequences all over the world and in all segments of the society. It is expected that waves of infections could continue until the epidemic is stopped by an effective vaccine. Currently, 30 vaccine studies are underway globally at various clinical trial stages, in addition to more than 100 on-going pretrial studies. Vaccine development, which usually takes over a decade, has been expedited thanks to new technologies that trigger protective immune response without risking the of infection.
The research team at the National Institute of Chemistry has become engaged in vaccine development, and now reports the results of the vaccine design and testing on mice. The results were published in the article which has been made publicly available at the bioRxiv server prior to review.
The vaccine has been designed based on plasmid DNA, which codes for a domain of a viral protein, and causes the production of those domains in human cells, which in turn triggers the formation of antibodies and protective T cells. Plasmid DNA-based Covid19 vaccines are currently being tested also in clinical trials in the USA, Japan, and South Korea. The advantage of using plasmid DNA is low production cost, high stability, which does not require a cold chain, while the disadvantage is less efficient uptake into cells, compared to viral systems.
According to the team from the Department of Synthetic Biology and Immunology at the National Institute of Chemistry, the novelty of their approach is the modification of viral proteins into self-assembling nanoparticles that resemble viruses, and thereby improving the immune system’s response. Five variants of the RBD viral protein domain responsible for cell receptor recognition have been prepared, that compose from 1 to 60 copies of RBD per particle. The preparation of virus-like particles is already established in the development of modern vaccines, but different methods for the formation of nanoparticle-based vaccines (two of which are original designs) have not been compared so far. The results of testing the immune response in mice against vaccines showed that the variant where a short beta annulus coding segment was added to the viral protein performed best. In this case, the response was more than a hundred fold better than the monomeric protein which is otherwise used by some other vaccines. Sera from mice have been shown to neutralise viral binding to the human receptor at concentrations comparable to other vaccines and from convalescent patients. In addition, they showed the formation of T cells that destroy cells that produce viral proteins, which can also block the infection.
Scheme: Molecular models of five types of Covid-19 vaccine prepared by the researchers from the Department of Synthetic Biology and Immunology at the National Institute of Chemistry.
Link to animation with model structures: https://l12-ki.owncube.com/index.php/s/nXByWAbefKgqe8T
The researchers point out that the results of preclinical studies are only in the initial stage, and that there is still a long way to go before the vaccine could be used, as extensive clinical trials are required, and several vaccines at advanced clinical trial stage around the world are showing promising results. Nevertheless, they believe that the results are encouraging to continue until the effective, affordable, and safe vaccine is available. For the next steps, a consortium has been organised in Slovenia, where in addition to the National Institute of Chemistry, researchers from the Faculty of Veterinary Medicine, the Faculty of Pharmacy UL, Physicians from the University Medical Centra and Golnik University Hospital, and the company Jafral, will prepare a process for vaccine production for clinical trials, and the documentation for approval of the clinical trial in accordance with the high requirements for administering the vaccine to humans. Slovenian researchers were aided with reagents from colleagues from Switzerland and Germany.
“The greatest importance of the presented research is in my opinion the development of a new technology that will be useful, not only for this virus, but also for vaccines against other viruses in the future. It is important that we have organised an interdisciplinary group capable of translating the results of the research into the clinical use. I hope we will be able to develop a Slovenian drug through this collaboration, and make it available for patients. I am proud of my colleagues, who have devoted exceptional energy and capabilities to this challenging project, thus proving that we can make a small contribution to the fight against this crucial problem of humanity and infectious diseases,” said the research team leader, Prof. Dr. Roman Jerala.
“The research team at the National Institute of Chemistry, led by Prof. Dr. Roman Jerala, started intensive development of the SARS-CoV-2 vaccine after the Covid-19 spread to Europe. . The team of researchers led by Prof. Jerala ranks among the world recognized scientific; therefore, I believe that a vaccine made using the technology of this research team will be effective, and I hope that it will demonstrate an appropriate level of safety.” Prof. Dr. Borut Štrukelj commented that “with the current positive results, the group of researchers led by Prof. Dr. Roman Jerala has joined the top leading biotechnological groups developing a new vaccine with new original technologies“.
Prof. Dr. Gregor Anderluh added that the National Institute of Chemistry has been working on some other Covid-19-related research as well. These mainly focus on understanding the structure and function of the coronavirus, and the approaches to a rapid coronavirus detection. Anderluh emphasised that he was pleased that the Institute was able to adjust its research capacities so promptly, and was looking forward to continuing the research presented. “I hope that this will be recognised at national level, with appropriate investments in these research areas, in science in general, and of course, in response to Covid-19. At the EU pledging conference in early May, Slovenia pledged funds for Covid-19 research, and hopefully this good intent will be realised,” underlined Anderluh.
Researchers and authors of the publication are Dr. Duško Lainšček, Dr. Tina Fink, Dr. Vida Forstnerič, Dr. Iva Hafner-Bratkovič, Sara Orehek, Žiga Strmšek, Dr. Mateja Manček-Keber, Peter Pečan, Hana Esih, Špela Malenšek, Dr. Jana Aupič, Petra Dekleva, Tjaša Plaper, Sara Vidmar, Dr. Lucija Kadunc, Dr. Mojca Benčina, Neža Omersa, Dr. Gregor Anderluh, and Dr. Roman Jerala.
Link to the Article: https://www.biorxiv.org/content/10.1101/2020.08.28.244269v1