New Study Supports Llama Nanobodies As Potential COVID-19 Treatment

The llama is more known as a pop icon, less so as the source of a potential COVID-19 treatment.

In a latest study conducted by researchers at the Rosalind Franklin Institute in Oxfordshire, the tiny antibodies generated in llama, also known as nanobodies, were demonstrated to effectively neutralize the SARS-CoV-2 virus in animal models. The study, published in Nature Communications, suggests the therapy could be developed as a nasal spray to treat or even prevent early infection. 

Nanobodies from Fifi, the Llama

Nanobodies are smaller, simpler antibodies generated in response to infection by camelids like alpacas, camels, and llamas. The team managed to obtain nanobodies from Fifi, a llama residing at the antibody production facility at the University of Reading.

They first injected a portion of the spike protein, which is found on the surface of SARS-CoV-2. The spikes themselves are not infectious, but the viral particles prompt the immune system to generate nanobodies in response. The team then took a blood sample from Fifi and tested for nanobodies that bind most strongly to the virus.

How Nanobodies Work Against COVID-19?

The spike protein binds to angiotensin-converting enzyme 2 (ACE2) receptors on human cells. This binding allows the virus to enter and infect the cell.

Nanobodies bind to the receptor binding domain (RBD) on the spike protein, thereby blocking the spike from interacting with ACE2 and preventing viral entry.

The researchers picked four nanobody chains with the highest affinities for the spike protein. Further, they combined each nanobody chain into groups of three, forming trimers. This boosted the ability of the chains to bind to the virus.

The nanobody chains exhibited strong binding to the original virus, as well as the Alpha and Beta variants. However, the researchers did not conclusively say whether the nanobodies work on the Delta variant. 

From Llama to Hamsters 

Next, the team tested the efficacy of the nanobodies on the Syrian golden hamster, which has been used as an animal model for COVID-19 research. When they administered a single intranasal dose (0.4mg/kg) of nanobodies to the infected hamsters, there was a notable reduction in disease.

In a week, the treated hamsters lost far less weight compared to the untreated group. Furthermore, the treated group had a lower viral load in their lungs and airways compared to the untreated hamsters. The animal study implies that treatment with nanobodies could reduce the infectivity and severity of the virus. 

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

Prof Carroll added that the nanobodies were “among the most effective SARS-CoV-2 neutralizing agents we have ever tested at PHE”. 

Cheaper to Produce, No Need for Needles

Professor Ray Owens, who heads protein production at the Rosalind Franklin Institute, listed the advantages of nanobodies over human antibodies. “They are cheaper to produce and can be delivered directly to the airways through a nebuliser or nasal spray, and can be self-administered at home rather than needing an injection,” he said. The researchers hope to obtain funding for more preclinical studies, which could pave the way for human trials. 

ExeVir’s Nanobodies In Phase 1 Trials 

The team at Rosalind Franklin Institute is not the first to work on llama-derived nanobodies as a treatment for COVID-19.  ExeVir Bio, a Belgium-based biotech, has already advanced into a Phase 1 clinical trial with its lead candidate, XVR011.

XVR011 also blocks the spike protein from binding to ACE2. It was derived from another llama, Winter, in 2016. To increase its efficiency and prevent dissociation in the bloodstream, the researchers from Belgium fused the original nanobody to human immunoglobulin G (IgG).

If approved, these nanobodies can provide an alternative and convenient form of treatment for COVID-19 patients, besides existing antibody cocktails such as Regeneron’s REGEN-COV and Eli-Lilly’s antibody combo.

Author

Joy Lin

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