Image source: Institute for Research in Biomedicine
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.
The work has been published in the journal Nature.
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 bispecificLuca Varani
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.”
“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.
Source: Institute for Research in Biomedicine