Llama Antibodies Have “Significant Potential” As Frontline COVID-19 Treatment – Simple Nasal Spray

A unique type of small antibody produced by llamas could provide a new first-line treatment against Covid-19 that can be taken by patients as a simple nasal spray.

Research led by scientists at the Rosalind Franklin Institute has shown that nanobodies — a smaller, simple form of antibody generated by llamas and camels — can effectively target the SARS-CoV-2 virus that causes Covid-19.

They found that short chains of the molecules, which can be produced in large quantities in the lab, significantly reduced signs of Covid-19 disease when administered to infected animal models.

The nanobodies, which bind tightly to the SARS-CoV-2 virus and neutralize it in cell culture, could provide a cheaper and easier-to-use alternative to human antibodies collected from patients who have recovered from Covid-19. Human antibodies have been an important treatment for severe cases during the pandemic, but usually have to be infused through a needle in the hospital.

Public Health England has described the research as having “significant potential for both the prevention and treatment of Covid-19”, adding that the nanobodies are “among the most effective SARS-CoV-2 neutralizing agents we have ever tested.”

“Nanobodies have a number of advantages over human antibodies,” said Professor Ray Owens, chief of protein production at the Rosalind Franklin Institute and lead author of the study. “They are cheaper to produce and can be delivered directly into the airways via a nebulizer or nasal spray, so they can be self-administered at home rather than needing an injection. This can have benefits in terms of ease of use by patients, but the also delivers the treatment directly to the site of infection in the respiratory tract.”

The research team, whose findings are published in the journal Nature Communication, were able to generate the nanobodies by injecting part of the SARS-CoV-2 spike protein into a llama called Fifi, which is part of the antibody production facility at the University. of reading.

The spike protein is on the outside of the virus and is responsible for binding to human cells so that it can infect them.

While the injections didn’t make Fifi sick, it activated her immune system to fight the virus protein by generating nanobodies against it. A small blood sample was then taken from the llama and the researchers were able to purify four nanobodies that can bind to the Covid-19 virus.

The nanobodies were then assembled into chains of three to increase their ability to bind to the virus. These were then produced in cells in the lab.

The team found that three nanobody chains were able to neutralize both the original Covid-19 virus variants and the Alpha variant first identified in Kent, UK. A fourth nanobody chain was able to neutralize the beta variant first identified in South Africa.

When one of the nanobody chains – also called trimer – was administered to hamsters infected with SARS-CoV-2, the animals showed a marked reduction in disease and lost much less weight after seven days than those left untreated. . Hamsters that received the nanobody treatment also had a lower viral load in their lungs and airways after seven days than untreated animals.

“Because we can see every atom of the nanobody on the spike, we understand what makes these agents so special,” said Professor James Naismith, director of the Rosalind Franklin Institute, who led the research.

The results are the first step towards developing a new type of treatment against Covid-19, which could prove invaluable as the pandemic continues.

“While vaccines have proven extremely successful, not everyone responds to vaccination and immunity can decline in individuals at different times,” said Professor Naismith. “Having drugs that can treat the virus will still be very important, especially as the whole world is not being vaccinated at the same rate and there remains a risk of new variants emerging that can boost vaccine immunity.” bypass.”

If successful and approved, nanobodies could provide an important treatment worldwide because they are easier to produce than human antibodies and do not need to be kept in cold storage facilities, Professor Naismith added.

The research team, which included scientists from the University of Liverpool, the University of Oxford and Public Health England, now hopes to secure funding so they can conduct further research needed to prepare for clinical trials in humans.

Prof Miles Carroll, Deputy Director of the National Infection Service, Public Health England (PHE), said: “While this research is still in its early stages, it offers significant potential for using effective nanobody treatments for COVID-19 .

“These are among the most effective SARS-CoV-2 neutralizers we’ve 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 together to advance this work in clinical trials.”

dr. Andrew Bourne, Director of Partnerships at EPSRC, said:

“Using the unique properties of llamas nanobodies, this research could lead to an important new form of treatment for Covid-19 that is cheaper to produce and easier to administer.

“It is a vivid illustration of the impact that long-term discovery research can have at the intersection of physical and life sciences, as conducted at the Rosalind Franklin Institute.”

Professor James Stewart, co-author and professor of molecular virology at the University of Liverpool, said: “The preclinical trials of the nanobodies in hamsters are extremely encouraging and suggest they could be effective in treating COVID-19 disease as well as help prevent infection. Having such therapies will be important for populations that have not been vaccinated or where vaccination is inappropriate or ineffective.”

The researchers, who were funded by the UK Research and Innovation’s Medical Research Council and the Engineering and Physical Sciences Research Council, The EPA Cephalosporin Fund and Wellcome, also hope that the nanobody technology they’ve developed could form a so-called “platform technology” that can be quickly adapted to fight other diseases.

“If a new virus shows up in the future, the generic technology we’ve developed can respond to it, which would be important to produce new treatments as quickly as possible,” said Professor Owens.

Reference: “A potent SARS-CoV-2 neutralizing nanobody demonstrates therapeutic efficacy in the Syrian golden hamster model of COVID-19” September 22, 2021, Nature Communications.
DOI: 10.1038/s41467-021-25480-z