Bellinzona, 25.01.2021 – The Institute for Research in Biomedicine (IRB; Bellinzona, Switzerland), affiliated to the Università della Svizzera italiana (USI) developed a second-generation ‘double antibody’ that protects from SARS-CoV-2, the virus causing COVID-19, and all its tested variants. It also prevents the virus from mutating to resist the therapy.
Antibody-based immunotherapy was already shown to be effective against COVID-19 but faces two main obstacles: it needs to work against the circulating viral variants; it must prevent formation of new variants, that can rapidly ensue via a mechanism similar to that leading to antibiotic resistant bacteria. We solved the problem by joining two natural antibodies into a single artificial molecule, called ‘bispecific antibody’, that targets two independent viral sites simultaneously.
Pre-clinical trials showed that this bispecific antibody potently neutralizes SARS-CoV-2 and its variants, including the recent UK one circulating in Switzerland and Europe with increased spread. The bispecific, but not first-generation antibodies, prevents the virus from changing its structure to evade therapy. The high bispecific potency and its overall characteristics make it an ideal candidate for human clinical trials, with good chances of employment both for prevention and treatment of COVID-19.
“We exploited our knowledge of the molecular structure and biochemical traits of the virus to fuse together two human antibodies, obtaining a single bispecific molecule simultaneously attacking the virus in two independent sites critical for infectivity”, said Luca Varani, group leader at the IRB and author of the scientific work. “Supercomputing simulations allowed us to refine and validate the bispecific antibody design, which was later produced and tested in the laboratory. Although the virus can mutate and escape from the attack of a single first-generation antibody, we have shown that it cannot do so against the double action of the bispecific’.
Davide Robbiani, IRB director and co-author of the scientific work, commented:” IRB and Ticino consolidate their position among the world leaders in antibody discovery and development, especially against emerging and neglected infectious diseases. Despite the limited resources, in comparison to big-pharma, we achieved our goals in just a few months’.
“A single injection of the bispecific antibody provides instantaneous protection against the disease in pre-clinical trials. The antibody effectively reduces viral burden in the lungs and mitigates inflammation typical of COVID-19”, said Daniel Ruzek from the Czech Academy of Sciences who led the antibody pre-clinical testing.
The bispecific antibody was developed within the research consortium ATAC, funded last April from the European Commission in response to the COVID-19 pandemic. Other members include San Matteo Hospital in Pavia (Italy), Karolinska Institutet (Sweden), Braunschweig University (Germany) and the Joint Research Centre of the European Commission. Collaboration with Rockfeller University and the Czech Academy of Science was instrumental to prove the bispecific efficacy.
The Institute for Research in Biomedicine (IRB) in Bellinzona, affiliated to the Università della Svizzera italiana (USI) performed basic research for more than 20 years. Financed by private and public institutions, and by competitive grants, the IRB currently hosts 13 research groups and 125 researchers that investigate the mechanisms of host defence against infectious agents, cancer and degenerative diseases. Currently, the research activities extend beyond immunology to include the fields of DNA repair, rare diseases, structural and cell biology. With more than 720 publications in leading scientific journals, the IRB has gained an international reputation as a centre of excellence in human immunology. www.irb.usi.ch
More info on the ATAC project
This work is presently under review and has been posted on the pre-print server bioRxiv:
Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease
Raoul De Gasparo, Mattia Pedotti, Luca Simonelli, Petr Nickl, Frauke Muecksch, Julio C. C. Lorenzi, Federica Mazzola, Davide Magrì, Tereza Michalcikova, Jan Haviernik, Vaclav Honig, Irene Cassaniti, Elena Percivalle, Blanka Mrazkova, Natalie Polakova, Andrea Fortova, Jolana Tureckova, Veronika Iatsiuk, Salvatore Di Girolamo, Martin Palus, Dagmar Zudova, Petr Bednar, Ivana Bukova, Filippo Bianchini, Dora Mehn, Radim Nencka, Petra Strakova, Oto Pavlis, Jan Rozman, Sabrina Gioria, Josè Camilla Sammartino, Federica Giardina, Stefano Gaiarsa, Qiang Pan Hammarström, Christopher O. Barnes, Antonio Piralla, Pamela J. Bjorkman, Fausto Baldanti, Luigi Calzolai, Michel C. Nussenzweig, Paul D. Bieniasz, Theodora Hatziioannou, Jan Prochazka, Radislav Sedlacek, Davide F. Robbiani, Daniel Ruzek, Luca Varani