Could Fifi the Llama Help in Developing a COVID Nasal Spray?

Peter Russell

September 22, 2021

Scientists say they might have discovered a new frontline treatment against COVID-19 using a unique type of antibody produced by llamas and camels.

Research by the Rosalind Franklin Institute has shown that nanobodies from the animals can be produced in large quantities in the laboratory to reduce signs of the disease in early trials.

Scientists predict the technique could be used to combat COVID using a nasal spray and provide a cheaper alternative to human antibodies taken from patients who have recovered from the disease.

In animal experiments, they found that the nanobodies bind tightly to the SARS-CoV-2 virus, neutralising it in cell culture.

Nasal Sprays

"The small molecular size and stability of nanobodies allows them to be formulated for topical delivery directly to the airways of infected patients through aerosolisation," researchers write in the journal Nature Communications.

"Nanobodies have a number of advantages over human antibodies,” said Professor Ray Owens, head of protein production at the Rosalind Franklin Institute and lead author of the research.

"They are cheaper to produce and can be delivered directly to the airways through a nebuliser or nasal spray, so can be self-administered at home rather than needing an injection.

"This could have benefits in terms of ease of use by patients but it also gets the treatment directly to the site of infection in the respiratory tract."

The trial involved a llama called Fifi who was injected with a portion of the SARS-CoV-2 spike protein. The researchers said the injections did not make Fifi sick but triggered her immune system to fight off the COVID-19 virus by generating nanobodies against it. 

They took a blood sample from the llama to purify four nanobodies capable of binding to the COVID-19 virus. These were then combined into chains of three to increase their ability to bind to the virus.

The researchers found three nanobody chains were able to neutralise both the original variants of SARS-CoV-2 and the Alpha variant, while a fourth nanobody chain was able to neutralise the Beta variant.

Next, the team administered the nanobodies to hamsters infected with SARS-CoV-2, and noted a reduction in disease, shown by minimal weight loss and limited pulmonary changes, along with lower viral loads, compared with those who did not receive the treatment.

'Significant Possibilities'

"Because we can see every atom of the nanobody bound to the spike, we understand what makes these agents so special,” said Prof James Naismith, director of the Rosalind Franklin Institute, who co-authored the research.

Prof James Stewart, co-author and professor of molecular virology at the University of Liverpool commented: "The pre-clinical trials of the nanobodies in hamsters are extremely encouraging and suggest that they may be effective at treating COVID-19 disease as well as help prevent infection."

Prof Miles Carroll, deputy director of the National Infection Service at Public Health England (PHE), said: "Although this research is still at an early stage, it opens up significant possibilities for the use of effective nanobody treatments for COVID-19.

"These are among the most effective SARS-CoV-2 neutralising agents we have ever tested at PHE. We believe the unique structure and strength of the nanobodies contribute to their significant potential for both the prevention and treatment of COVID-19, and look forward to working collaboratively to progress this work into clinical studies."

The research was funded by the Rosalind Franklin Institute and the Engineering and Physical Sciences Research Council, with support from the EPA Cephalosporin Fund, and the Wellcome Trust.

A potent SARS-CoV-2 neutralising nanobody shows therapeutic efficacy in the Syrian golden hamster model of COVID-19. Nature Communications volume 12, Article number: 5469 (2021) 

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Lead Image: PA Media

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