Llama, Llama—What’s All This Antibody Drama?

By Armaan Singh


Image Credit: Pexels @ Trace Hudson

As a child I used to read this funny book titled Llama Llama Red Pajama by Anna Dewdney. I always viewed llamas as a charming albeit useless creature. However, in times of peril and uncertainty, llamas may pose a solution to a problem that has brought world leaders to their knees. Whereas a vast majority of animals produce antibodies similar to our own, some animals produce antibodies differing in size from humans. Llamas happen to be one such animal with unique sized antibodies. Llama, llama--this is a potentially game changing finding! Before delving deeper into the specifics, let’s first go over the broader discussion about antibodies.


Antibodies are generally described as a protein in the blood with a main focus on identifying, combining, and neutralizing alien antigens such as viruses. In most animals, antibodies function the same way. However, the key difference between antibodies that occur in human blood and in the blood of llamas is not function, but rather another variable: size. The concept of antibodies and antigen binding is similar to jigsaw puzzles where each specific piece can align with the pieces around it and effectively fills the space on the board. My biology teacher aptly compared antibodies to biological handcuffs of sorts that are able to immobilize and allow other cells to identify the invader. The challenge with coronavirus is the presence of a key protein or spike protein that causes Covid-19. Finding an antibody to bind tightly to the dense pack of spike proteins has been perplexing.


Animals such as llamas produce two types of antibodies: one that is similar to humans and one other that is of a much smaller size. The smaller sized antibodies are called “single-domain” antibodies. Creatures from the Camelidae family (including llamas and camels) have special types of antibodies known as “single-domain” antibodies or nanobodies. Nanobodies have key differential properties that make them a potential treatment of Covid-19. They are a quarter of the size of a human antibody and possess significantly more stability than ours. As a result of this heightened stability, the antibodies are also more easily stored. Nanobodies have been called ‘warheads’ in the fight against Covid-19 as they add to the arsenal of potential treatments. For example, they can also be turned into a dry powder and be aerosolized (substances converted into particles small and light enough to be transferred through the air) directly into the lungs, which is especially useful because Coronavirus is a respiratory disease. However, not only does size vary in the equation, but shape as well.

In llama antibodies, the small size and pointed shape make it more ideal for treating coronavirus in contrast to the larger and bulkier human antibodies that are harder to work with in this area of treatment. To test this hypothesis, scientists injected spike proteins (the spikes found on the surface of Covid-19) inside a llama’s bloodstream which have a tendency to latch onto and fuse with the cell. Upon fusing, the virus divides rapidly and produces more infected cells. It was interestingly noted that the antibodies successfully bind to the protein before the rapid multiplication. Another study that is a confirmation of these results comes from research in Belgium under the guidance of Peter Walter and Aashish Manglik. Walter and Manglik found that llama’s antibodies are similarly apt at combating viruses such as SARS, which is extremely similar in various aspects to Coronavirus. As a matter of fact, the antibody was so pertinent in its stability and binding capabilities that Walter compared it to a mousetrap.


The future of antibody research has great long and short term potential. In laboratory experiments, there has been progress in the creation of engineered “nanobodies” from llamas that bind strongly to SARS–Cov2 and stop the virus from entering cells. Time will tell how great of an impact llama antibodies will have in the treatment of Covid-19, yet it has opened up a vast frontier of research and exploration. So, the next time you curl up and reach for that children’s book on your shelf--remember that there is some truth and a little magic to that bedtime story about llamas.




What did you learn?

Question:

1. Why is research being explored on Llama nanobodies?


Answer:

Animals from the Camelidae family (including llamas and camels) have special types of antibodies known as “single-domain” antibodies or nanobodies. Nanobodies have key differential properties that make them a potential treatment of Covid-19; they are a quarter of the size of a human antibody and possess significantly more stability than our antibodies. Nanobodies have been called ‘warheads’: in the fight against Covid-19, they add to the arsenal of potential treatments out there.


Question:

2. How have scientists used llama antibodies for research with Covid-19?


Answer:

Scientists injected spike proteins (the spikes found on the surface of Covid-19) inside a llama’s bloodstream which have a tendency to latch onto the cell and fuse with the cell. Upon fusing, the virus divides rapidly and produces more infected cells. After investigating the results, it was a pleasant surprise that the antibodies successfully bind to the protein before the rapid multiplication.




Citations

https://www.statnews.com/2020/08/11/scientists-create-potent-anti-coronavirus-nanobody-inspired-by-llamas/

https://www.inverse.com/science/animal-antibody-experiments-explained

https://www.nih.gov/news-events/nih-research-matters/llama-antibody-engineered-block-coronavirus


Image Credit:

https://www.pexels.com/photo/photo-of-llama-during-daytime-2847475/

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