UK researchers have used antibodies derived from llamas to neutralise the SARS-CoV-2 virus in lab tests.
The team involves researchers from the Rosalind Franklin Institute, Oxford University, Diamond Light Source and Public Health England.
They hope the antibodies – known as nanobodies due to their small size – could eventually be developed as a treatment for patients with severe COVID-19.
The llama link
Llamas, camels and alpacas naturally produce quantities of small antibodies with a simpler structure, that can be turned into nanobodies.
The team engineered their new nanobodies using a collection of antibodies taken from llama blood cells. They have shown that the nanobodies bind tightly to the spike protein of the SARS-CoV-2 virus, blocking it from entering human cells and stopping infection.
Using advanced imaging with X-rays and electrons at Diamond Light Source and Oxford University, the team also identified that the nanobodies bind to the spike protein in a new and different way to other antibodies already discovered.
There is currently no cure or vaccine for COVID-19. However, transfusion of critically ill patients with serum from convalesced individuals, which contain human antibodies against the virus, has been shown to greatly improve clinical outcome.
This process, known as passive immunisation, has been used for over 100 years, but it is not straightforward to identify the right individuals with the right antibodies and to give such a blood product safely.
A lab-based product which can be made on demand would have considerable advantages and could be used earlier in the disease where it is likely to be more effective.
“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,” said Professor James Naismith, Director of The Rosalind Franklin Institute and Professor of Structural Biology at Oxford University
“We were able to combine one of the nanobodies with a human antibody and show the combination was even more powerful than either alone. 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.”
The team started from a lab-based library of llama antibodies. They are now screening antibodies from Fifi, one of the ‘Franklin llamas’ based at the University of Reading, taken after she was immunised with harmless purified virus proteins.
The team are investigating preliminary results which show that Fifi’s immune system has produced different antibodies from those already identified, which will enable cocktails of nanobodies to be tested against the virus.
The peer reviewed findings are published in Nature Structural & Molecular Biology.