The Paul Ehrlich and Ludwig Darmstaedter Prize 2022 has been awarded to Katalin Karikó (pictured left), University of Pennsylvania, Philadelphia, USA, Özlem Türeci (pictured center), and Uğur Şahin (pictured right), both BioNTech SE, Mainz, Germany. The three researchers are honored for their achievements in the development of messenger RNA (mRNA) for preventive and therapeutic purposes. This technology has, for example, played a key role in the rapid development of a highly effective vaccine against COVID-19.
The Paul Ehrlich and Ludwig Darmstaedter Prize is Germany’s most renowned medical award and comes with an endowment of EUR 120,000. It is traditionally awarded on Paul Ehrlich’s birthday, March 14, in the Paulskirche in Frankfurt am Main, Germany. The award honors scientists who have made special contributions in areas of research related to Paul Ehrlich’s achievements, i.e., in immunology, cancer research, hematology, microbiology, or chemotherapy.
Research
mRNAs are messenger molecules that carry genetic information from the DNA in the cell nucleus to the ribosomes in the cytoplasm, where the information is used to construct proteins. Unlike DNA therapeutics, mRNA does not have to enter the cell’s nucleus to exert its effect and does not integrate into the genome of its target cell.
In contrast to DNA, mRNA is very unstable. In addition, our immune system normally regards externally applied mRNA as an unwanted intruder, which can inhibit the translation of externally derived mRNA. Karikó achieved a decisive breakthrough here: She discovered how to blunt the body’s own defense response against synthetic mRNA, and consequently, how to significantly increase intracellular protein production.
Uğur Şahin and Özlem Türeci focused on developing cancer vaccines, including truly individualized ones, to present a patient’s immune system with the antigens of their own tumor to stimulate target-specific effects. They aimed to solve the basic mRNA-associated problem of short-lived protein production. They developed a series of optimized designs for various structural components of mRNA, thereby significantly increasing both its intracellular stability and its translational efficiency. They further improved vaccine efficacy via strategies to deliver RNA into dendritic cells located in lymphoid tissues using a lipid nanoparticle formulation.
These breakthrough improvements formed the basis for the successful use of mRNA for various human applications. During the last years, BioNTech has made significant progress in the clinical application of cancer vaccines. The knowledge gained in the development of cancer vaccines also decisively contributed to the rapid availability of a COVID-19 mRNA vaccine. The non-immunogenic mRNA modifications Karikó discovered made it easier to develop a highly effective COVID-19 vaccine in a comparably short time.
Katalin Karikó
Katalin Karikó, born on January 17, 1955, in Szolnok, Hungary, studied biology at the University of Szeged, where she received her Ph.D. in 1982. After a postdoctoral stay at the Biological Research Centre (BRC) of the Hungarian Academy of Sciences, Szeged, she moved to the United States in 1985. She was a postdoctoral fellow at Temple University, Philadelphia, PA, USA, from 1985 to 1988, and at the Uniformed Services University of the Health Sciences, Bethesda, MD, USA, from 1988 to 1989. Karikó serves as Senior Vice President of BioNTech AG in Mainz, Germany, as Professor at the University of Szeged, and as an Adjunct Professor of Neurosurgery at the University of Pennsylvania.
Katalin Karikó has received numerous awards, including the Japan Prize in 2022, the Breakthrough Prize in Life Sciences 2022, the Széchenyi Prize 2021, the Wilhelm Exner Medal in 2021, the Semmelweis Prize 2021, the Princess of Asturias Award 2021, and the Rosenstiel Award in 2020, and is a Member of the Academia Europaea.
Özlem Türeci
Özlem Türeci was born in Siegen, Germany, in 1967. She studied medicine at Saarland University in Homburg, Germany, and received her doctorate in 1992. She completed her habilitation at the University of Mainz in 2002. Starting in 2001, she served as CEO and Chief Medical Officer of Ganymed Pharmaceuticals AG. Türeci is Co-Founder and Chief Medical Officer of BioNTech. She also serves as Professor for Personalized Immunotherapy at the University Medical Center Mainz and the Helmholtz Institute for Translational Oncology Mainz (HI-TRON) and as President of the Association for Cancer Immunotherapy (CIMT) in Germany.
Among many other honors, Türeci has received the German Sustainability Award in 2020, the Order of Merit of the Federal Republic of Germany, the Princess of Asturias Award in the category Scientific Research, the Aydın Doğan Award, the William B. Coley Award from the Cancer Research Institute, New York, USA, and the German Future Prize, all in 2021.
Uğur Şahin
Uğur Şahin was born in İskenderun, Turkey, in 1965. He studied medicine at the University of Cologne, Germany, where he completed his doctorate in 1992. He completed his habilitation in molecular medicine and immunology in 1999. Starting in 2001, he worked at the University Medical Center Mainz. He serves as Professor in Translational Oncology & Immunology at the University of Mainz. He holds the role of Chairman of the Scientific Management Board of the Helmholtz Institute for Translational Oncology (HI-TRON), also in Mainz. He is Co-Founder and CEO of BioNTech.
Şahin has received numerous awards and recognitions, including the Merit Award of the American Society of Oncology in 1995, the Calogero Paglierello Research Award in 1997, the Georges Köhler Prize from the German Society of Immunology in 2005, the Mustafa Prize and the German Cancer Award in 2019, the German Sustainability Award in 2020, the Order of Merit of the Federal Republic of Germany, the Princess of Asturias Award in the category Scientific Research, the William B. Coley Award, and the German Future Prize, all in 2021.
Selected Publications
- Ribozyme Assays to Quantify the Capping Efficiency of In Vitro-Transcribed mRNA,
Irena Vlatkovic, János Ludwig, Gábor Boros, Gábor Tamás Szabó, Julia Reichert, Maximilian Buff, Markus Baiersdörfer, Jonas Reinholz, Azita Josefine Mahiny, Uğur Şahin, Katalin Karikó,
Pharmaceutics 2022, 14, 328.
https://doi.org/10.3390/pharmaceutics14020328 - An Fc-inert PD-L1x4-1BB bispecific antibody mediates potent anti-tumor immunity in mice by combining checkpoint inhibition and conditional 4-1BB co-stimulation,
Alexander Muik, Isil Altintas, Friederike Gieseke, Kristina B. Schoedel, Saskia M. Burm, Aras Toker, Theodora W. Salcedo, Dennis Verzijl, David Eisel, Christian Grunwitz, Lena M. Kranz, Mathias Vormehr, David P. E. Satijn, Mustafa Diken, Sebastian Kreiter, Kate Sasser, Tahamtan Ahmadi, Özlem Türeci, Esther C. W. Breij, Maria Jure-Kunkel, Uğur Şahin,
OncoImmunology 2022.
https://doi.org/10.1080/2162402X.2022.2030135 - Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine–elicited human sera,
Alexander Muik, Bonny Gaby Lui, Ann-Kathrin Wallisch, Maren Bacher, Julia Mühl, Jonas Reinholz, Orkun Ozhelvaci, Nina Beckmann, Ramón de la Caridad Güimil Garcia, Asaf Poran, Svetlana Shpyro, Andrew Finlayson, Hui Cai, Qi Yang, Kena A. Swanson, Özlem Türeci, Uğur Şahin,
Science 2022, 375, 678–680.
https://doi.org/10.1126/science.abn7591 - Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents,
Robert W. Frenck, Nicola P. Klein, Nicholas Kitchin, Alejandra Gurtman, Judith Absalon, Stephen Lockhart, John L. Perez, Emmanuel B. Walter, Shelly Senders, Ruth Bailey, Kena A. Swanson, Hua Ma, Xia Xu, Kenneth Koury, Warren V. Kalina, David Cooper, Timothy Jennings, Donald M. Brandon, Stephen J. Thomas, Özlem Türeci, Dina B. Tresnan, Susan Mather, Philip R. Dormitzer, Uğur Şahin, Kathrin U. Jansen, William C. Gruber,
N. Engl. J. Med. 2021, 385, 239–250.
https://doi.org/10.1056/NEJMoa2107456 - Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomized, placebo-controlled, double-blind phase 1 study,
Jingxin Li, Aimin Hui, Xiang Zhang, Yumei Yang, Rong Tang, Huayue Ye, Ruiru Ji, Mei Lin, Zhongkui Zhu, Özlem Türeci, Eleni Lagkadinou, Siyue Jia, Hongxing Pan, Fuzhong Peng, Zhilong Ma, Zhenggang Wu, Xiling Guo, Yunfeng Shi, Alexander Muik, Uğur Şahin, Li Zhu, Fengcai Zhu,
Nat. Med. 2021, 27, 1062–1070.
https://doi.org/10.1038/s41591-021-01330-9 - Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models,
Christian Hotz, Timothy R. Wagenaar, Friederike Gieseke, Dinesh S. Bangari, Michelle Callahan, Hui Cao, Jan Diekmann, Mustafa Diken, Christian Grunwitz, Andy Hebert, Karl Hsu, Marie Bernardo, Katalin Karikó, Sebastian Kreiter, Andreas N. Kuhn, Mikhail Levit, Natalia Malkova, Serena Masciari, Jack Pollard, Hui Qu, Sue Ryan, Abderaouf Selmi, Julia Schlereth, Kuldeep Singh, Fangxian Sun, Bodo Tillmann, Tatiana Tolstykh, William Weber, Lena Wicke, Sonja Witzel, Qunyan Yu, Yu-An Zhang, Gang Zheng, Joanne Lager, Gary J. Nabel, Uğur Şahin, Dmitri Wiederschain,
Sci. Transl. Med. 2021.
https://doi.org/10.1126/scitranslmed.abc7804 - MO24-1 Phase I/IIa trial evaluating safety and clinical activity of DuoBody®-PD-L1×4-1BB (GEN1046) in advanced solid tumors,
Ignacio Melero, Ravit Geva, Eytan Ben-Ami, Corinne Maurice-Dror, Emiliano Calvo, Patricia LoRusso, Özlem Türeci, Michelle Niewood, Uğur Şahin, Maria Jure-Kunkel, Ulf Forssmann, Tahamtan Ahmadi, Guzman Alonso,
Ann. Oncol. 2021, 32, S313.
https://doi.org/10.1016/j.annonc.2021.05.625 - Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses,
Mohamad-Gabriel Alameh, István Tombácz, Emily Bettini, Katlyn Lederer, Chutamath Sittplangkoon, Joel R. Wilmore, Brian T. Gaudette, Ousamah Y. Soliman, Matthew Pine, Philip Hicks, Tomaz B. Manzoni, James J. Knox, John L. Johnson, Dorottya Laczkó, Hiromi Muramatsu, Benjamin Davis, Wenzhao Meng, Aaron M. Rosenfeld, Shirin Strohmeier, Paulo J.C. Lin, Barbara L. Mui, Ying K. Tam, Katalin Karikó, Alain Jacquet, Florian Krammer, Paul Bates, Michael P. Cancro, Drew Weissman, Eline T. Luning Prak, David Allman, Michela Locci, Norbert Pardi,
Immunity 2021, 54, 2877–2892.e7.
https://doi.org/10.1016/j.immuni.2021.11.001 - Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine,
Fernando P. Polack, Stephen J. Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, John L. Perez, Gonzalo Pérez Marc, Edson D. Moreira, Cristiano Zerbini, Ruth Bailey, Kena A. Swanson, Satrajit Roychoudhury, Kenneth Koury, Ping Li, Warren V. Kalina, David Cooper, Robert W. Frenck, Laura L. Hammitt, Özlem Türeci, Haylene Nell, Axel Schaefer, Serhat Ünal, Dina B. Tresnan, Susan Mather, Philip R. Dormitzer, Uğur Şahin, Kathrin U. Jansen, William C. Gruber,
N. Engl. J. Med. 2020, 383, 2603–2615.
https://doi.org/10.1056/NEJMoa2034577 - Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates,
Edward E. Walsh, Robert W. Frenck, Ann R. Falsey, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, Kathleen Neuzil, Mark J. Mulligan, Ruth Bailey, Kena A. Swanson, Ping Li, Kenneth Koury, Warren Kalina, David Cooper, Camila Fontes-Garfias, Pei-Yong Shi, Özlem Türeci, Kristin R. Tompkins, Kirsten E. Lyke, Vanessa Raabe, Philip R. Dormitzer, Kathrin U. Jansen, Uğur Şahin, William C. Gruber,
N. Engl. J. Med. 2020, 383, 2439–2450.
https://doi.org/10.1056/NEJMoa2027906 - Personalized vaccines for cancer immunotherapy,
Uğur Şahin, Özlem Türeci,
Science 2018, 359, 1355–1360.
https://doi.org/10.1126/science.aar7112 - Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer,
Uğur Şahin, Evelyna Derhovanessian, Matthias Miller, Björn-Philipp Kloke, Petra Simon, Martin Löwer, Valesca Bukur, Arbel D. Tadmor, Ulrich Luxemburger, Barbara Schrörs, Tana Omokoko, Mathias Vormehr, Christian Albrecht, Anna Paruzynski, Andreas N. Kuhn, Janina Buck, Sandra Heesch, Katharina H. Schreeb, Felicitas Müller, Inga Ortseifer, Isabel Vogler, Eva Godehardt, Sebastian Attig, Richard Rae, Andrea Breitkreuz, Claudia Tolliver, Martin Suchan, Goran Martic, Alexander Hohberger, Patrick Sorn, Jan Diekmann, Janko Ciesla, Olga Waksmann, Alexandra-Kemmer Brück, Meike Witt, Martina Zillgen, Andree Rothermel, Barbara Kasemann, David Langer, Stefanie Bolte, Mustafa Diken, Sebastian Kreiter, Romina Nemecek, Christoffer Gebhardt, Stephan Grabbe, Christoph Höller, Jochen Utikal, Christoph Huber, Carmen Loquai, Özlem Türeci,
Nature 2017, 547, 222–226.
https://doi.org/10.1038/nature23003 - mRNA-based therapeutics — developing a new class of drugs,
Uğur Şahin, Katalin Karikó, Özlem Türeci,
Natu. Rev. Drug Discov. 2014, 13, 759–780.
https://doi.org/10.1038/nrd4278 - Incorporation of Pseudouridine Into mRNA Yields Superior Nonimmunogenic Vector With Increased Translational Capacity and Biological Stability,
Katalin Karikó, Hiromi Muramatsu, Frank A. Welsh, János Ludwig, Hiroki Kato, Shizuo Akira, Drew Weissman,
Mol. Ther. 2008, 16, 1833–1840.
https://doi.org/10.1038/mt.2008.200 - Sequence- and target-independent angiogenesis suppression by siRNA via TLR3,
Mark E. Kleinman, Kiyoshi Yamada, Atsunobu Takeda, Vasu Chandrasekaran, Miho Nozaki, Judit Z. Baffi, Romulo J. C. Albuquerque, Satoshi Yamasaki, Masahiro Itaya, Yuzhen Pan, Binoy Appukuttan, Daniel Gibbs, Zhenglin Yang, Katalin Karikó, Balamurali K. Ambati, Traci A. Wilgus, Luisa A. DiPietro, Eiji Sakurai, Kang Zhang, Justine R. Smith, Ethan W. Taylor, Jayakrishna Ambati,
Nature 2008, 452, 591–597.
https://doi.org/10.1038/nature06765 - Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells,
Silke Holtkamp, Sebastian Kreiter, Abderraouf Selmi, Petra Simon, Michael Koslowski, Christoph Huber, Özlem Türeci, Uğur Şahin,
Blood 2006, 108, 4009–4017.
https://doi.org/10.1182/blood-2006-04-015024
Also of Interest
- Interview with Ingmar Hoerr, Pioneer of mRNA Technology,
Vera Koester, Ingmar Hoerr,
ChemistryViews 2021.
https://doi.org/10.1002/chemv.202100030
As a Ph.D. student, Hoerr discovered that mRNA can be used as a therapeutic vaccine or agent when administered directly into tissues - Clever Picture: Comparing COVID-19 Vaccines
