Engineered Llama Antibodies Neutralise COVID-19 Virus, Say UK Researchers

Priscilla Lynch 

July 22, 2020

Antibodies (nanobodies) derived from llamas have been shown to neutralise the SARS-CoV-2 virus in laboratory tests by UK researchers. The peer reviewed findings are published in Nature Structural & Molecular Biology.

Llamas, camels and alpacas naturally produce quantities of small antibodies with a simpler structure, which can be turned into nanobodies. The research team engineered nanobodies using a naive llama single-domain antibody library and polymerase chain reaction-based maturation and used purified receptor binding domain (RBD) of the SARS-CoV-2 spike to identify its binding partners by in vitro phage display technology.

The study reports the identification and charactersation of two closely related high-affinity nanobodies (H11-D4 and H11-H4) that blocked the attachment of the spike to angiotensin-converting enzyme 2 (ACE2) in vitro.

Using advanced imaging with X-rays and electrons, the team identified that the nanobodies bind to the spike protein in a new and different way to other antibodies already discovered. Both nanobodies inhibited the binding of both RBD and spike to ACE2. This suggested the nanobody epitope overlaps with the ACE2 binding site on the RBD of spike.

Both nanobodies, when fused to immunoglobulin-G Fc, neutralised live virus, with H11-H4-Fc showing a particularly high potency (50% neutraliation dose of 4-6 nM). H11-H4 also showed additive neutralisation with CR3022.

The nanobodies may have application on their own or in additive combinations with other antibodies in the treatment of severely ill COVID-19 patients, the researchers said.

Study author Prof James Naismith, Professor of Structural Biology at Oxford University and Director of The Rosalind Franklin Institute, said: “These nanobodies have the potential to be used in a similar way to convalescent serum, effectively stopping progression of the virus in patients who are ill. We were able to combine one of the nanobodies with a human antibody and show the combination was even more powerful than either alone.”

Huo J, Le Bas A, Ruza RR, Duyvesteyn HME, Mikolajek H, Malinauskas T, Tan TK, Rijal P, Dumoux M, Ward PN, Ren J, Zhou D, Harrison PJ, Weckener M, Clare DK, Vogirala VK, Radecke J, Moynié L, Zhao Y, Gilbert-Jaramillo J, Knight ML, Tree JA, Buttigieg KR, Coombes N, Elmore MJ, Carroll MW, Carrique L, Shah PNM, James W, Townsend AR, Stuart DI, Owens RJ, Naismith JH. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2. Nat Struct Mol Biol. 2020 July 13 [Epub ahead of print]. doi: 10.1038/s41594-020-0469-6. PMID: 32661423 Full text.

This article originally appeared on Univadis, part of the Medscape Professional Network.

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