ImmunoSensation2 member Florian I. Schmidt together with Paul-Albert König, head of the Nanobody Core Facility and an international team have identified and further developed novel antibody fragments against the SARS coronavirus-2.
These "nanobodies" are much smaller than the classic antibodies used to treat SARS-CoV-2 infections, for example. They therefore penetrate the tissue better and can be produced more easily in larger quantities. The researchers at the University Hospital Bonn have also combined the nanobodies into potentially particularly effective molecules. These attack different parts of the virus simultaneously. The approach could prevent the pathogen from evading the active agent through mutations. The results are published in the journal Science.
"We focus on another group of molecules, the nanobodies," explains Dr. Florian Schmidt, who heads an Emmy Noether group on this promising new field of research at the University of Bonn's Institute of Innate Immunity. "Nanobodies are antibody fragments that are so simple that they can be produced by bacteria or yeast, which is less expensive."
The researchers also exploit another major advantage of nanobodies over antibodies: Their simple structure allows straight forward combinations to form molecules that can be several hundred times more effective. "We have fused two nanobodies that target different parts of the spike protein," explains König. "This variant was highly effective in cell culture. Furthermore, we were able to show that this drastically reduces the probability of the virus to become resistant to the active agent through escape mutations." The researchers are convinced that the molecules may be developed into a novel and promising therapeutic option.
Dioscure Therapeutics, a spin-off of the University of Bonn, will test the nanobodies in clinical studies. The success of the project is mainly based on the excellent cooperation of the participating research groups at the University with national and international cooperation partners, emphasizes Florian Schmidt.
Publication
Paul-Albert König, Hrishikesh Das, Hejun Liu, Beate M. Kümmerer, Florian N. Gohr, Lea-Marie Jenster, Yonas M. Tesfamariam, Lisa D.J. Schiffelers, Miki Uchima, Jennifer D. Wuerth, Karl Gatterdam, Natalia Ruetalo, Maria H. Christensen, Caroline I. Fandrey, Sabine Normann, Steffen Pritzl, Jan M. P. Tödtmann, Leo Hanke, Jannik Boos, Meng Yuan, Xueyong Zhu, Jonathan Leo Schmid-Burgk, Hiroki Kato, Michael Schindler, Ian A. Wilson, Matthias Geyer, Kerstin U. Ludwig, B. Martin Hällberg, Nicholas C. Wu and Florian I. Schmidt: Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape. Science; DOI: 10.1126/science.abe6230
Contact
Institute of Innate Immunity
University Hospital Bonn
University of Bonn
Email: fschmidt@uni-bonn.de
Phone office: +49-228/287-51124
Phone lab: +49-228/287-54708
Cell: +49-176/70021810
