Second generation antibody protects from SARS-CoV-2, its variant and prevents it from mutating to resist therapy
Czech researchers have tested a new “double antibody” which very effectively protects humans against coronavirus SARS-CoV-2 and all its tested variants. At the same time, it also prevents the virus from mutating and becoming resistant to treatment. The antibody was developed by Swiss scientists from the Institute for Research in Biomedicine (IRB), and their Czech colleagues from the Biological Centre of the Academy of Sciences of the Czech Republic. The Czech Centre for Phenogenomics at BIOCEV tested the antibody's effectiveness in a preclinical study.
To develop a new active substance, Swiss researchers used antibodies obtained from patients who had been afflicted by covid-19. Antibody-based therapy is effective, but it faces two main problems: on the one hand, the antibody must act against the currently occurring variants of the virus and, on the other hand, it must prevent viral mutations that would increase the virus's resistance, as is the case with bacteria that become resistant to the antibiotics being used. "We solved the problem by combining two natural antibodies into one molecule called a bispecific antibody, which targets two different viral sites at the same time," said Luca Varani, team leader at the Swiss IRB Institute. The targeting of two independent sites in the structure of the virus is quite innovative and prevents the virus from developing resistance to treatment. "Although the virus can mutate to avoid a single antibody attack, we have shown that it cannot escape the double action of our bispecific molecule," Luca Varani explained. Using supercomputer simulations, the researchers then refined the molecule and conducted a preclinical study for laboratory testing.
This has been carried out since November 2020 in the laboratories of the Biological Centre of the ASCR in České Budějovice under strict high degree BSL-3 security conditions. The study confirmed that the bispecific antibody effectively neutralizes the SARS-CoV-2 coronavirus and its variants, including the recent British mutation. The combined efficacy and overall characteristics thus make the new antibody the ideal candidate for a human clinical study. It might not only support the treatment of a patient with a weak immune response but could also act as an effective prophylactic. "In an animal model of covid-19, a single injection of bispecific antibody provided immediate protection against the disease, which can last for weeks or months. The antibody effectively reduces the viral load in the lungs and reduces inflammation," confirmed Daniel Růžek from the Biological Centre of the ASCR and the Research Institute of Veterinary Medicine, which conducted the preclinical testing of antibodies in animals.
A mouse model sensitive to SARS-CoV-2 infection was prepared by scientists at the Czech Centre for Phenogenomics, one of the many research infrastructures at the BIOCEV centre, after speaking with virologists who were not able to find a suitable model. This is because normal laboratory mice cannot be used for coronavirus research as they are relatively resistant to the disease. "The mouse model developed by us is relatively unique and economical and closely represents severe cases of the disease that we have observed in humans, such as inflammatory responses in the lungs and the like," said Radislav Sedláček, head of the Czech Centre for Phenogenomics (The Institute of Molecular Genetics AS CR at the BIOCEV centre).
The Research Institute of Veterinary Medicine in Brno, the Institute of Organic Chemistry and Biochemistry in Prague and the Military Medical Institute in Těchonín also took part in the preclinical study. The success of Czech scientists in the field of coronavirus research and their immediate effective involvement in the fight against the pandemic proves that Czech know-how offers promising potential. In the Czech Republic, however, virological research is fragmented into smaller laboratories in several institutions and there is still a lack of suitable infrastructure at the national level that can unify it and provide an adequate basis for further developing it. The necessary impetus could be provided by the intended Virological Centre, for which the Academy of Sciences of the Czech Republic is negotiating support at the government level.
Picture: The bispecific antibody was developed within the ATAC research consortium, funded by the European Commission in April 2020 in response to the COVID-19 pandemic. Other members include San Matteo Hospital in Pavia (Italy), the Karolinska Institute (Sweden), Braunschweig University (Germany) and the Joint Research Centre of the European Commission.
Pictured left: The mouse model for Covid-19 infection created at the Czech Centre for Phenogenomics reacts to Sars-Cov-2 infection manifesting in a very severe course of the disease in which a large part of the lung tissue is affected. Therefore, the effect of therapeutic antibodies developed by Swiss scientists, with which Sars-Cov-2-infected mice resisted infection and almost no lung damage occurred, is so fascinating (pictured right) Source: The Czech Centre for Phenogenomics (The Institute of Molecular Genetics AS CR, BIOCEV).
Publication preprint: https://www.biorxiv.org/content/10.1101/2021.01.22.427567v1