Researchers engineer new nanobodies from Ilama blood cells against COVID-19 infection

UK scientists declared recently that antibodies extracted from llamas have been demonstrated to neutralize the SARS-CoV-2 virus in laboratory tests.

The team includes scientists from the Rosalind Franklin Institute, Diamond Light Source, Oxford University, and Public Health England. They consider that the antibodies—called nanobodies because of their small size—could finally be developed as a treatment for patients with severe COVID-19. The peer-reviewed results of the study have been reported in the Nature Structural & Molecular Biology journal.

By nature, alpacas, camels, and llamas produce considerable quantities of small antibodies that have a simpler structure. These antibodies can be converted into nanobodies. The researchers used a group of antibodies derived from llama blood cells to design their new nanobodies. They have demonstrated that the nanobodies attach tightly to the spike protein of the SARS-CoV-2 virus, thereby inhibiting it from entering human cells and preventing infection.

Sophisticated imaging with X-rays and electrons at Diamond Light Source and Oxford University was used by the researchers to find that the nanobodies attach to the spike protein in a new and unique way compared to already discovered antibodies.

At present, there is no vaccine or treatment for COVID-19. But the transfusion of serum from convalesced individuals, which contains human antibodies against the virus, to critically ill patients has been demonstrated to considerably enhance clinical results.

Dubbed passive immunization, this process has been used for about 100 years; however, it is not easy to find the right individuals with the ideal antibodies and to safely administer such a blood product. A laboratory-based product that can be produced when needed would offer considerable benefits and could be used earlier in the disease where it could be more powerful.

These nanobodies have the potential to be used in a similar way to convalescent serum, effectively stopping progression of the virus in patients who are ill. We were able to combine one of the nanobodies with a human antibody and show the combination was even more powerful than either alone.”

James Naismith, Director, Rosalind Franklin Institute, and Professor, Department of Structural Biology, Oxford University

Naismith added, “Combinations are particularly useful since the virus has to change multiple things at the same time to escape; this is very hard for the virus to do. The nanobodies also have potential as a powerful diagnostic.”

This research is a great example of team work in science, as we have created, analyzed and tested the nanobodies in 12 weeks. This has seen the team carry out experiments in just a few days that would typically take months to complete. We are hopeful that we can push this breakthrough on into pre-clinical trials.”

Ray Owens, Professor, Oxford University

Owens also leads the nanobody program at the Rosalind Franklin Institute.

According to Professor David Stuart from Diamond Light Source and Oxford University, “The electron microscopy structures showed us that the three nanobodies can bind to the virus spike, essentially covering up the portions that the virus uses to enter human cells.”

The researchers started their study from a laboratory-based library of llama antibodies. At present, they are screening antibodies from Fifi, one of the “Franklin llamas” from the University of Reading, extracted after she was immunized with safe purified virus proteins.

The team has been analyzing the initial results, which demonstrate that Fifi’s immune system has produced various antibodies different from those already recognized, which will allow cocktails of nanobodies to be tested against the virus.

“2020 marks the centenary of Franklin’s birth. As an institute named for a pioneer of biological imaging, we are proud to follow in her footsteps and continue her work in viruses, applied here to an unprecedented global pandemic. Franklin’s work transformed biology, and our projects aspire to that same transformational effect,” Professor Naismith concluded.