• Although vaccines are highly effective in preventing COVID-19, scientists still need to identify better treatments for the disease.
• Some scientists are investigating whether llama-derived antibodies might be a useful treatment approach.
• A recent study has shown that so-called nanobodies that scientists harvested from a llama reduced SARS-CoV-2 viral load in Syrian hamsters.

In the race to discover effective treatments for COVID-19, some scientists have turned to using antibodies from people who have recovered from COVID-19.

Although this approach has seen some success, these treatments tend to be difficult to manufacture and expensive.

A recent study, which appears in the journal Nature Communications, investigates a type of antibody derived from a llama. The authors hope that this approach will be simpler and more cost effective.

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Targeted nanobodies

Members of the camelid family, which includes camels, llamas, and alpacas, produce unique antibodies called nanobodies. Nanobodies are extremely small, robust, and stable molecules that bind to specific targets.

This targeted attachment makes nanobodies ideally suited to many forms of research, especially those involving the detection and neutralization of viruses.

The authors of the recent study investigated the nanobodies of a llama named Fifi.

The scientists injected Fifi with a purified bioprotein that did not cause illness but prompted her immune system to produce nanobodies. They then extracted these molecules from a small sample of Fifi’s blood.

The team isolated four different nanobodies and designated them as C5, F2, H3, and C1. Laboratory tests showed that each of these nanobodies bonds to distinct locations on the spike protein.

When the C5 nanobodies were configured in trimers — consisting of three C5’s in a row — the researchers observed a complete inhibition of viral infection.

They then tested the C5 trimer in 12 Syrian golden hamsters that had the SARS-CoV-2 infection. After 1 day, they treated six with an injection of the C5 trimer nanobody, while the remaining six — the controls — received no treatment.

All of the animals lost weight during the study. However, by day 7, the six hamsters in the nanobody-treated group had lost significantly less weight. Indeed, as the authors explain, those that received the single dose of C5 nanobodies showed “minimal weight loss and very limited pulmonary infection.”

Further testing using the COVID-19 hamster model indicated that the nasal administration of nanobody treatment promoted a faster recovery from infection than administration by injection. The authors believe that this might be because it was easier for the nanobodies to reach the site of infection — the lungs.

Study summary and future steps

Prof. James Naismith is the director of the Rosalind Franklin Institute, the United Kingdom’s national health research institute and one of the organizations that supported this study.

Prof. Naismith summarizes some of the potential benefits of the nanobody approach:

• These nanobodies appear to be potent against key strains of the SARS-CoV-2 virus.
• Due to their tiny size, the trimers are easy to administer because it is possible to inhale them.
• Scientists can make the trimer cheaply in simple systems, such as yeast and Escherichia coli.

Speaking with Medical News Today, Elitza Theel, Ph.D., director of the Infectious Diseases Serology Laboratory at Mayo Clinic, Rochester, MN, said:

“It would be worthwhile to see the therapeutic effect of these nanoantibodies in nonhuman primates. [This study’s] findings on the use of intranasal administration of anti-RBD nanoantibodies are quite intriguing, as they show significant protection against disease similar to intraperitoneal injection in their Syrian [hamster] model.”

At a recent press conference, in response to a question about the next steps required to move these findings to human trials, Prof. Raymond Owens, Protein Production U.K. principal scientist at the Nuffield Department of Medicine, responded:

“We are working with manufacturing organizations who can take our lab-scale process and scale it up so that we can produce sufficient quantities and quality of material. And then we need to understand a little bit more about the behavior of the molecule in animal models.”

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