The secret to stopping Covid-19 could lie in the blood of llamas. The claim is not as surprising to immunologists as it might be to everyone else, since they are familiar with the exceptional antibodies produced by llamas and alpacas. Nevertheless, the discovery of the effectiveness of two small llama antibodies in neutralizing SARS CoV-2 could be an important step in the quest to end the pandemic.
Llamas and alpacas produce a type of small antibody called nanobodies that differ from those seen in humans and most other mammals. They contain a single chain of proteins rather than the double chain ours possess. Nanobodies are effective tools for distinguishing between some viruses, and since they are stable and easy to produce they are widely used by the diagnostic industry. Back in the more innocent days of 2016, a llama called Winter was injected with spike proteins from the two previous deadly coronaviruses, SARS-CoV-1 and MERS-CoV, and produced antibodies that might block the entry of these viruses into human cells.
In May, scientists announced one of Winter's antibodies, VHH-72, binds to SARS-CoV-2 in culture and that an engineered version does so much more effectively, preventing the virus from entering cells.
Now a team from the Rosalind Franklin Institute and the University of Oxford have shown this is not a one-off; other llama antibodies also block the virus in culture, but do so with a different mechanism from those previously found to neutralize SARS-1. In Nature, they note that “SARS-CoV-2 spike binds to ACE2 with a 10- to 20-fold higher affinity (KD of ~15nM) than SARS-CoV-1 spike, a fact that has been proposed to drive its higher transmissibility.”
The paper reports the nanobodies H11-D4 and H11-H4 show a strong affinity to the SARS-CoV-2 spike, as if llamas had spent a long time adapting to this disease, instead of being as new to it as we are. These nanobodies bind to part of the spike adjacent to the area it uses to bind to ACE2 receptors in the cells of its victims.
When the virus is added to a culture containing human cells, H11-D4 and H11-H4 prevent it from getting inside those cells to multiply. Even at very low concentrations, they proved able to neutralize 50 percent of the virus particles from entering cells.
Neutralization in culture is no guarantee of success within the human body, but the authors are optimistic these llama antibodies could interrupt the virus enough to reduce the severity of the disease, possibly in combination with other antibodies. Llama nanobodies usually prove stable inside the human body and are not seen by our own immune systems as a threat.
The paper acknowledges the fact that H11-H4 doesn't appear to be protective against SARS-CoV-1 and raises the risk of SARS-CoV-2 mutating to avoid this antibody. If that happens, however, they think we may find other llama antibodies that block the spike's mutated versions.