Filenews 6 August 2021
Mini antibodies that effectively neutralize the coronavirus and its variants have been created by researchers from the Mah Planck Institute in Gettygen Germany. Mini antibodies or nanosomes bind and neutralize the virus up to 1000 times better than previously developed antibodies, while remaining stable and withstanding extreme temperatures.
These characteristics, combined with their ability to be produced at low cost and in large quantities to meet the global demand for anti-coronae medicines, bring these nanosomes on the way to starting clinical trials.
Scientists at the Max Planck Institute and the Medical Center of the University of Gettygen, Germany, developed mini antibodies (VHH antibodies or nanosomes) that could be a drug against coronavirus disease.
As Max Planck Institute director Dr. Dick Gerlych points out, "for the first time, they combine exceptional stability and exceptional efficacy against the virus and its variants, Alpha, Beta, Gamma and Delta."
At first glance, the new nanosomes are not much different from the SARS-CoV-2 nanosomes developed by other laboratories. It all turns against a critical part of the coronavirus spike protein, the point at which the virus enters our body's cells. Nanosomes block the spike protein and thus prevent the virus from infecting the cells.
"Nanosomes can withstand temperatures of up to 95 degrees Celsius without losing function or forming agglomerations," explains Mathias Dobelstein, professor and director of the UMG Institute of Molecular Oncology. This indicates that they may remain active in the body long enough to be effective. On the other hand, heat-resistant nanosomes are easier to produce, process and store.".
Single, double and triple nanosomes
The simplest mini antibodies developed by The Gettygen team are already up to 1000 times more strongly associated with the spike protein than previous-generation nanosomes. They are also very well associated with mutated proteins – pins of alpha, beta, gamma and delta strains. 'Single nanosomes are potentially suitable for inhalation and therefore for immediate elimination of viruses in the respiratory tract. Moreover, because they are very small, they could easily penetrate the tissues and prevent the virus from spreading further," says Dobelstein.
A "trio of nanosomes" further improves virus binding: The researchers joined three identical nanosomes depending on the symmetry of the spike protein, which consists of three identical building blocks with three binding points. "The trio of nanomas is literally a union of forces. In an ideal scenario, each of the three nanosomes clings to one of the three binding points," says Thomas Gytler, a researcher on Gerlych's team. "This creates a theoretically irreversible bond. The triad will not let the spike protein release and neutralizes the virus even up to 30,000 times better than individual nanosomes." Another advantage is the larger size of the trio of nanomas, which delays as expected the response from the kidneys. This keeps them in the body for longer and promises long-term therapeutic action.
The third option is to produce different combination models. The scientists combined two nanosomes that target different parts of the binding receptor and together they can bind the spike protein. "Such combination patterns are extremely resistant to virus mutations and the 'immune escape' caused by mutations, because they are so powerfully binding to protein spike," explains Metin Aksu, a researcher on Gerlich's team.
In all of the above combination alternatives of nanosomas – single, double, triple – the researchers found that very small amounts are sufficient to stop the pathogen. If used as a drug, this will allow low dosage and therefore fewer side effects and lower production costs.
Alpacas provide mini antibodies
"These nanosomes come from alpacas and are smaller and simpler than conventional antibodies," says Gerlih. To create them, the researchers identified three female alpacas, Britta, Nora and Xenia, with parts of the coronae protein. Then the animals produced antibodies and the scientists took out a small blood sample and blood tests on humans," explains Gerlych.
Gerlich's team made about a billion plans for nanosomes from alpaca blood. The biochemists then used bacteriophages to select the best nanosomes, which were tested for their effectiveness, as not every antibody is "neutralizing".
As a result, Dobelstein's team investigated how nanosomes prevent viruses from reproducing in cultured cells in the lab. Less than a millionth of a gram per litre of cultivation was enough to completely prevent contamination. In the case of triple nanomas, an additional dilution of 20 times more was sufficient'.
