COVID-19 vaccine shows the long-term value of curiosity-driven basic research

The most promising vaccine against the coronavirus to date is also an example of the long-term value of curiosity-driven basic research and its funding by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).

The so-called mRNA vaccine platform, which the Mainz-based company BioNTech uses in its Covid-19 vaccine developed jointly with the US pharmaceutical company Pfizer, can be traced back to preliminary work carried out from 2006 to 2008 in a project within a DFG-funded Collaborative Research Centre (CRC) on cancer research at the Johannes Gutenberg University Mainz. This in turn was also tied to previous DFG-funded research.

The project was led by the later founder and current CEO of BioNTech, Professor Dr. Uğur Şahin, whose name and person are closely associated with the development of the BNT162b2 vaccine, which will be deployed immediately following its approval in the United Kingdom and its anticipated approval in the USA and the EU.

In addition to him, Privatdozent Dr. Özlem Türeci, Şahin's wife, who as Chief Medical Officer of BioNTech is also significantly involved in the Covid-19 vaccine, conducted research in a project in the Collaborative Research Centre.

The spokesperson of the CRC was immunologist and oncologist Professor Dr. Christoph Huber, who was also one of the subsequent founders of BioNTech and is now a member of the company's supervisory board.

Şahin describes the work funded by the DFG as "important contributions" towards exploring fundamental scientific issues on the path to the currently deployed mRNA vaccine platform. "That preliminary work helped lay the foundations for the development of our vaccine," states Şahin.

The CRC in which Şahin conducted his work received funding of approximately €19 million from 1997 to 2008. He conducted research on "mechanisms of tumor defense and their therapeutic implications" in two major areas with more than a dozen projects each. Şahin was initially involved in the CRC as of 2000 as the head of an independent junior research group.

He received further funding in a Research Training Group from 2004, just like Özlem Türeci, who was granted a habilitation fellowship and funded under the DFG's Heisenberg Programme.

Şahin's project was set up in 2006 in the final funding period for the CRC and initially led by him as a Privatdozent before he was appointed to a professorship in experimental oncology. The project received over €300,000 in funds before the CRC ended in 2008.

Under the title "Development of mRNA-based vaccines to induce integrated T- and B-cell immune responses against molecularly defined tumor antigens," the project aimed to control and destroy tumors by directly activating the body's own immune system, which is a fundamentally different approach to therapy than radiation or chemotherapy.

This approach involves the tumor antigens on the surface of tumor cells being identified and their genetic information deciphered. The genetic blueprint obtained in this way can then be used as a template or platform for the development and technological production of a vaccine specifically directed to target tumor antigens.

Ribonucleic acids (mRNA) are used as a vaccine substance. They inform the immune system about the tumor antigens to be combated and then rapidly degrade, thus leaving no permanent genetic changes in the genome.

This approach of so-called mRNA vaccination is in turn based on other preliminary work from the 1990s. This included work in a Collaborative Research Centre at the University of Tübingen funded by the DFG from 1997 to 2004.

Co-workers in the CRC led by immunologist Professor Dr. Hans-Georg Rammensee on the main topic entitled "Stem cells and antigen recognition in the hematopoietic system. From hematopoietic stem cells to immunotherapy" included, among others, Dr. Ingmar Hoerr, who obtained his doctorate there within a project and then went on to found the biotech company Curevac, which is also currently working to develop a coronavirus vaccine.

Şahin himself continued the work started in the CRC within the framework of several grants from the German Federal Ministry of Education and Research (BMBF) and in the DFG-funded Research Centre Translational Oncology (TRON), which he co-founded in 2010, at Mainz University Medical Centre, and, since 2008, in his spin-off BioNTech, where this work has now contributed to the development of the coronavirus vaccine.

The immune system has evolved over millions of years to provide us with optimum protection against pathogens, such as viruses. Our early research addressed the question of how we can further improve these immune mechanisms and use them to fight cancer cells. Now we've been able to build on this knowledge. Using a vaccine to activate the immune system against SARS-CoV-2 is in comparison an easier challenge than overcoming self-tolerance against cancer."

Dr. Uğur Şahin, Professor and Later Founder, Current CEO of BioNTech

"The years we spent crossing the borders between basic research and application also served us well. It is never a one-way process, but rather the findings from basic research constantly stimulate translation - just as application-oriented research provides findings and raises new questions, which then have to be studied again from a basic research perspective," concludes Şahin.

In addition to his activity at BioNTech, the researcher continues to be a Professor of Experimental Oncology at the University of Mainz and continues to receive DFG funding as a project head in three CRCs that are currently ongoing.

DFG President Professor Dr. Katja Becker congratulated Şahin and his staff on the development of their vaccine, stating: "The DFG is very pleased to have had the opportunity of making its contribution to the early findings. These are now being used in the successful university spin-off which developed the vaccine that promises so much hope. Its development reveals the essential nature of research that derives knowledge solely based on scientific curiosity, and whose true value often lies in the very fact that it is unpredictable. No one could have foreseen the coronavirus pandemic when the CRC was established, and yet the research conducted at that time created a pool of knowledge which - years later and in a quite different area - is enabling significant progress to be made in combating this global challenge."

"This principle of curiosity-driven research, to which the DFG is especially committed, has been promoted in Germany for over 100 years and is once again proving to be a success story," continued Becker and referred to the founding of the DFG's predecessor organization "Notgemeinschaft der Deutschen Wissenschaft" in 1920, which the DFG is celebrating this year via its "DFG2020 - Because of Research Matters" campaign.

The DFG is the largest research funding organization in Germany and is currently funding more than 31,000 research projects in all subject areas. An annual budget of approximately €3.3 billion is available from the federal government and states and is allocated according to research quality criteria.

The spectrum of funding opportunities extends from an individual grant to major research networks. The latter is intended to enable the currently more than 270 Collaborative Research Centres to conduct research on long-term projects and to enhance the formation of core research areas and structures at universities.

The DFG also has a series of funding projects and other activities that are currently contributing directly to research relating to the coronavirus pandemic.

Even before the outbreak, there were around 20 research projects dealing with coronaviruses and the infectiousness and genetic diversity of viruses, including in several CRCs, a Clinical Research Unit, and a Priority Programme led by virologist Professor Dr Christian Drosten.

Only a few weeks after the outbreak of COVID-19, the DFG launched a large-scale call for multidisciplinary research into epidemics and pandemics.

This is intended to fund a wide range of research projects that extend from fundamental biological and medical aspects and preventive and therapeutic measures to psychological, social, cultural, legal, and ethical implications and the economy, logistics, and communication.

This call resulted in the DFG receiving almost 300 funding proposals and the first projects should be funded from the beginning of 2021.

In June, the DFG also established an interdisciplinary Commission for Pandemic Research that has 18 members from all research disciplines. Its role is to further enhance basic research in this field, support the pandemic call and the projects it funds, and to identify further areas of research.

Regarding this latter point, the DFG publishes specific calls that will enable so-called Focus Funding for a maximum of a year to fund projects dealing with questions that are particularly urgent or need to be answered at short notice.