Nasal spray treatment for COVID-19 in the works thanks to a llama named Fifi

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TORONTO — Scientists in the U.K. are developing a “potentially significant” treatment for COVID-19 that could be administered to patients in the form of a nasal spray, thanks to the tiny antibodies produced by a llama.

According to research from the Rosalind Franklin Institute, which was recently published in the journal Nature Communications, the treatment has the potential to prevent and treat COVID-19.

“While vaccines have proven extraordinarily successful, not everyone responds to vaccination and immunity can wane in individuals at different times,” James Naismith, director of the Rosalind Franklin Institute, who helped lead the research, said in a statement.

“Having medications that can treat the virus is still going to be very important, particularly as not all of the world is being vaccinated at the same speed and there remains a risk of new variants capable of bypassing vaccine immunity emerging.”

To develop the treatment, researchers injected a llama named Fifi with a tiny, non-infectious piece of purified spike protein from the SARS-CoV-2 virus – the virus that causes COVID-19.

The scientists chose a llama specifically because of the species’ unique ability to produce tiny single-domain antibodies – or nanobodies – in response to an infection. Other camelids including alpacas and camels, and even sharks, can produce these nanobodies too.

Due to their small size, these nanobodies are able to bind more tightly to the SARS-CoV-2 virus than larger antibodies produced by humans. Once the nanobodies have latched on to the invading virus, the body’s immune system flags it for destruction.

Steven Kerfoot, an associate professor of microbiology and immunology at Western University in London, Ont., who was not involved in the research, said the big advantage of these smaller nanobodies is their ability to squeeze into tight spaces on a virus protein. He also said they’re much easier to produce in a lab than human antibodies.

“It’s a lot easier to put together, a lot less complicated, and it's smaller, and can really sort of get into that binding spot quite well,” Kerfoot told CTVNews.ca during a telephone interview on Thursday. “So there are some real advantages for this particular approach.”

Ray Owens, head of protein production at the Rosalind Franklin Institute and lead author of the research, agreed the nanobodies have a number of advantages over human antibodies.

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

“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.”

Throughout the pandemic, human antibodies have been used to treat serious cases of COVID-19, but they typically need to be administered by intravenous infusion in the hospital. The nanobodies, on the other hand, could be delivered in the form of a simple nasal spray.

“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,” Owens added.

‘SIGNIFICANT POSSIBILITIES’

Returning to Fifi the llama, after the animal was injected with a small piece of the virus’ spike protein, its immune system was triggered to fight off the virus protein by generating nanobodies against it. Following this, the researchers took a sample of Fifi’s blood and purified four nanobodies from it that were capable of binding to the SARS-CoV-2 virus.

These nanobodies were then engineered in a lab into chains of three to increase their ability to bind to the virus.

Llamas have the unique ability to produce tiny single-domain antibodies – or nanobodies – in response to an infection. (Jo Kelly / Rosalind Franklin Institute)

The team found that three of the chains were able to neutralize the original variants of the SARS-CoV-2 virus and the Alpha variant, while a fourth chain was effective in neutralizing the Beta variant.

When one of the chains of nanobodies was tested in hamsters infected with COVID-19, the rodents showed a “marked reduction” in disease, lost far less weight than those that weren’t treated, and a had a lower viral load in their lungs and airways after seven days compared to those left untreated.

While the treatment has only been tested in animals, Public Health England said it was among the “most effective” SARS-CoV-2 neutralizing treatments they have ever tested.

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

Kerfoot said the idea of using antibodies from llamas and other animals in the camelid family is not new and has been in development for some time, but he’s not aware of its use in human treatment yet. He said the pandemic might provide the right impetus to further the research along, as it was for the mRNA technology now used in COVID-19 vaccines.

“If this becomes an approach that we can use to try and lessen the severity of respiratory viruses, there could be a lot of benefit to that. It's just not something that has made the leap to human treatment yet and this may be the push that sort of pushes it over that edge,” he said.

As for next steps, the team of researchers, which included scientists from the University of Liverpool, University of Oxford and PHE, are hoping to obtain funding in order to conduct clinical studies in humans. They also hope their nanobody technology might one day be used as a “platform technology” to fight off other diseases.

“When a new virus emerges in the future, the generic technology we have developed could respond to that, which would be important in terms of producing new treatments as quickly as possible,” Owens said.

Kerfoot agreed that there is a lot of potential to use this approach as a standard treatment for other airway diseases.

“There’s nothing special about SARS-CoV-2 that this approach wouldn't work for many of the other airway viruses,” he said. “I think there's certainly promise and the next step will have to be moving into human trials.”