Engineered llama antibodies neutralize COVID-19 virus

13-Jul-2020 2:40 PM EDT, by Rosalind Franklin Institute

Newswise — Antibodies derived from llamas have been shown to neutralise the SARS-CoV-2 virus in lab tests, UK researchers announced today.

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 peer reviewed findings are published in Nature Structural & Molecular Biology.

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.

Professor James Naismith, Director of The Rosalind Franklin Institute and Professor of Structural Biology at Oxford University said: "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."

Professor Ray Owens from Oxford University, who leads the nanobody program at the Franklin, said: "This research is a great example of team work in science, as we have created, analysed 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."

Professor David Stuart, from Diamond Light Source and Oxford University said: "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 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 Rosalind Franklin Institute is a new research institute funded through UK Research and Innovation's Engineering and Physical Sciences Research Council. The Franklin is leading the UK's work in the innovative field of nanobodies, whose tiny size and specificity make them perfect tools for scientific research, usually used to stabilise proteins for imaging. The Institute is named for the researcher Rosalind Franklin, who was born 100 years ago this year. Although famous for her contribution to the discovery of DNA, Franklin's later career turned to imaging virus structures, including polio.

Professor Naismith said: "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."

###

'Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2' by James H Naismith et al. is published in Nature Structural and Molecular Biology https://doi.org/10.1038/s41594-020-0469-6

The Rosalind Franklin Institute

The Rosalind Franklin Institute is a national institute dedicated to transforming life science through interdisciplinary research and technology development. The Institute will bring together researchers in life, physical science, and engineering, to develop disruptive new technologies designed to tackle major challenges in health and life sciences. Focussing initially on five major research themes, the Institute will have significant impact in imaging, diagnostics, drug development, and many more fields.

The Franklin is funded through the UK Research and Innovation through the Engineering and Physical Sciences Research Council (EPSRC). The Institute is an independent organisation founded by the UK Research and Innovation, ten UK universities, and Diamond Light Source, and will have its central hub at the Harwell Campus.

The Rosalind Franklin Institute is a company limited by guarantee registered in England and Wales, registration number 11266143. We are a Registered Charity, number 1179810.

Twitter: @RosFrankInst

http://www.rfi.ac.uk

About Diamond Light Source: http://www.diamond.ac.uk

Diamond Light Source is the UK's national synchrotron, providing industrial and academic user communities with access to state-of-the-art analytical tools to enable world-changing science. Shaped like a huge ring, it works like a giant microscope, accelerating electrons to near light speeds, to produce a light 10 billion times brighter than the Sun, which is then directed off into 33 laboratories known as 'beamlines'. In addition to these, Diamond offer access to several integrated laboratories including the Electron Bio-imaging Centre (eBIC) and the Electron Physical Science Imaging Centre (ePSIC).

Diamond serves as an agent of change, addressing 21st century challenges such as disease, clean energy, food security and more. Since operations started, more than 14,000 researchers from both academia and industry have used Diamond to conduct experiments, with the support of approximately 700 world-class staff. More than 9,000 scientific articles have been published by our users and scientists.

Funded by the UK Government through the Science and Technology Facilities Council (STFC), and by the Wellcome Trust, Diamond is one of the most advanced scientific facilities in the world, and its pioneering capabilities are helping to keep the UK at the forefront of scientific research.

The Engineering and Physical Sciences Research Council (EPSRC)

The EPSRC is the main funding body for engineering and physical sciences research in the UK. By investing in research and postgraduate training, we are building the knowledge and skills base needed to address the scientific and technological challenges facing the nation.

Our portfolio covers a vast range of fields from healthcare technologies to structural engineering, manufacturing to mathematics, advanced materials to chemistry. The research we fund has impact across all sectors. It provides a platform for future UK prosperity by contributing to a healthy, connected, resilient, productive nation.

EPSRC is part of UK Research and Innovation, a new body which works in partnership with universities, research organisations, businesses, charities, and government to create the best possible environment for research and innovation to flourish. We aim to maximise the contribution of each of our component parts, working individually and collectively. We work with our many partners to benefit everyone through knowledge, talent and ideas. For more information visit UK Research and Innovation.

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