Nanobodies engineered from llama antibodies show immunity against SARS-CoV-2

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A working group from The Rosalind Franklin Institute (Oxford, UK), Oxford University (UK), Diamond Light Source (Oxford, UK) and Public Health England (London, UK) have shown that their engineered antibodies – nanobodies – can effectively neutralize the SARS-CoV-2 virus in lab tests.

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The small nanobodies are based on llama (Lama glama) antibodies from llama blood cells, which have a less complex structure than human antibodies. Their work recently published in Nature Structural & Molecular Biology explains how the nanobodies bind tightly to the SARS-CoV-2 spike protein and effectively block it from entering host cells and causing infection.

When studying the nanobodies using advanced imaging techniques, the team found that they bind to the spike protein in a way unseen in other antibodies that have recently been discovered.

Professor David Stuart, from Diamond Light Source and Oxford University added: “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.”

Currently, antibodies have been used to treat COVID-19 in patients by transfusing critically ill patients with serum that contains human antibodies to the virus. This immunization method has improved the outcomes in these patients, however, is dependent on the compatibility of patients and the donors for the transfer of a blood product, to be successful. This means the scaled up use of this method is extremely difficult. By developing a lab-based immunization product the treatment could be distributed more widely and in a more timely fashion, even earlier in the disease progression, which would lead to increased effectiveness.

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James Naismith, Director of The Rosalind Franklin Institute and Professor at Oxford University stated: “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. 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 are investigating preliminary results, which show that the antibodies produced from the immune system of Fifi – a ‘Franklin llama’ kept at the University of Reading (UK) – are different compared to those already identified. This will allow many different combinations of nanobodies to be tested against the SARS-CoV-2 virus.

Ray Owens (Oxford University) who leads the nanobody program at the The Rosalind Franklin Institute, commented: “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.”

To see more on the development of these nanobodies, have a look at the interview with Ray Owens on our sister site, The Nanomed Zone, here >>>

Sources: Huo J, Le Bas A, Ruza RR et al. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2. Nat. Struct. Mol. Biol. doi:org/10.1038/s41594-020-0469-6 (2020) (Epub ahead of print); www.rfi.ac.uk/engineered-llama-antibodies-neutralise-covid-19-virus/

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