Llama-Based 'Antibody Cocktail' Neutralizes COVID-19 Virus

As Fifi the llama calmly munches on grass in a field in Reading, in southern England, she is completely oblivious to the fact that she is at the center of efforts to develop lifesaving immunotherapy to treat the most severe cases of the COVID-19 pandemic that's swept the globe.

Scientists from the UK's Rosalind Franklin Institute have created an immune-boosting therapy for COVID-19 using Fifi's specifically evolved antibodies. The resulting antibody therapy could enter clinical trials within months.

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Cutting a key to fit the coronavirus lock

Professor James Naismith, lead researcher and Director of the Rosalind Franklin Institute — which is developing the new technique in a collaboration with Oxford University, Diamond Light Source, and Public Health England — described the technique as the equivalent of cutting a key to fit the coronavirus lock.

"With the llama's antibodies, we have keys that don't quite fit - they'll go into the lock but won't turn all the way round," he told the BBC. "So we take that key and use molecular biology to polish bits of it, until we've cut a key that fits."

New nanobodies research tackling #COVID19 from Protein Production UK based at @RCatHarwell.

Done in collaboration with @UniofOxford, @OxfordStrubi, @DiamondLightSou and @PHE_uk.

Published today in @NatureSMB, find it here https://t.co/Fn4maUbOhq@HarwellCampus @EPSRC @The_MRC pic.twitter.com/OrJoGaoQ6t

— Rosalind Franklin Institute (@RosFrankInst) July 13, 2020

Antibodies are molecules that essentially morph in response to the body being attacked by a virus. "Then if you get re-infected," explained Prof Naismith, "your body looks for any [virus particles] with antibodies stuck around them and destroys them."

Evidence already supports the idea that antibodies from recovered COVID-19 patients can be used to treat sever patients using passive immunization, which gives them a line of defense against the disease.

So where do the llamas come in? 

Antibodies specifically derived from llamas have been shown to neutralize the SARS-CoV-2 virus in lab tests, the Rosalind Franklin Institute researchers led by Naismith have just revealed.

What's more, unlike traditional human antibody therapies, scientists can essentially use llamas to produce coronavirus-specific antibodies to order, using a method that extracts a small re-engineered part of the llama antibody also known as a nanobody.

"In the lab, we can make nanobodies that kill the live virus extremely well - better than almost anything we've seen," Naismith told the BBC. "They're incredibly good at killing the virus in culture."

The nanobodies are so effective because they can bind onto the "spike protein" on the outside of the SARS-COV 2 virus capsule and disable that spike from gaining access to human cells and causing infection.

A powerful combination of nanobodies and antibodies

"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," Naismith explained in a press release.

"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," he continued.

The team aims to test its new therapy in animal trials this summer, with the goal of commencing clinical trials later this year. Their peer-reviewed findings are published in Nature Structural & Molecular Biology. Worry not, no llamas were harmed in the scientist's research — Fifi is doing just fine and was immunized for the study with harmless purified virus proteins.