In Brief
- Llamas may present a unique solution to eliminating the COVID-19 pandemic. This is due to the extraordinary antibodies they produce.
- These animals generate antibodies that are much smaller than what is created by their human and other animal counterparts. From these antibodies, even smaller biological soldiers can be generated in the lab: so-called “nanobodies.”
- Nanobodies have astounding properties that make them a strong candidate to fight the coronavirus pandemic on a large scale.
Schools have been shut down. Hospitals have reached ICU capacity. At times, uncertainty and even panic have set in. With over 44 million cases and 1.1 million deaths, COVID-19 has changed our lives in unprecedented ways.
But could a lovable pack animal help change the trajectory of this deadly disease?
Most people know what llamas are. They’re large, camel-like creatures located predominantly in South America. However, what many don’t know is that llamas may present a unique solution to eliminating the COVID-19 pandemic. This is due to the extraordinary antibodies they produce. Antibodies are immune system proteins that defend humans and animals against foreign invaders. When pathogens like bacteria and viruses attack an organism, antibodies neutralize them.
In the late 1980s, scientists at the Free University of Brussels discovered something unusual about some of the antibodies that camels – which are evolutionarily-related to llamas – produce. These animals generate antibodies that are much smaller than what is created by their human and other animal counterparts. From these antibodies, even smaller biological soldiers can be generated in the lab: so-called “nanobodies.”
Despite their tiny physical nature, nanobodies have astounding properties that make them a strong candidate to fight the coronavirus pandemic on a large scale. Among these advantages are the ease in which they can be mass produced and stored for long time periods. In addition, nanobodies can be nebulized, meaning they can be delivered directly to the patient’s lungs via an inhaler where they can immediately attack the virus.
Researchers at the University of Texas, Austin in collaboration with the University of Ghent and VIB in Belgium sought to derive a treatment by injecting coronavirus spike proteins into a llama. They then studied the antibodies produced by the animal’s immune system to attack these foreign proteins. Using an advanced filtering technique, the researchers singled out a nanobody that was capable of preventing the virus from infecting human cells in the lab.
To grasp how this therapy works, one must first understand how a virus infects a human. The virus latches onto a host cell, which for the coronavirus is a cell in a person’s airway. The virus then fuses with that cell. Next, the virus injects its genetic material into the cell and uses the host’s gene-making machinery to massively replicate itself many times over. Bursting out of this makeshift factory, newborn viruses venture outward and take control of many more cells. When enough cells are conquered, a person will typically become ill and contagious.
Our immune systems use antibodies that bind to the invader before it can infect the host cell to counter viral attacks. Antibodies act like bodyguards, blocking the virus from the host cell and protecting the individual from illness. The U.S. and Belgian researchers are hoping to give the immune systems of COVID-19 patients an added boost by using llama nanobodies to provide an extra line of defense.
To enhance the effectiveness of these llama-based nanobodies, researchers merged them with part of a human antibody. This helps the human immune system recognize it and not label it as a foreign substance. The engineered modification also allows the antibody to more-strongly bind to the virus, giving researchers confidence that it will be a potent virus fighter.
In order for this treatment to be accepted for patient use, it must first undergo rigorous testing to ensure safety and effectiveness. The first round of testing in animals is currently underway at the University of Ghent, where researchers are evaluating how well it works in hamsters.
“If the results from the hamster trials look good, then we will move into nonhuman primates, such as rhesus monkeys and if that works, we can start clinical trials in humans,” says University of Texas graduate student Daniel Wrapp, who is leading the llama nanobody investigation.
Wrapp’s research partner in Belgium, Xavier Saelens, Ph.D., adds, “Perhaps early in 2021 the llama-derived drug could be evaluated in a phase 1 clinical trial. We can’t predict that it will work in humans. We are very confident and optimistic, but it’s to be proven.”
Among the concerns voiced by Saelens, Wrapp and their colleagues are possible side effects of this treatment. “The human immune system is so interconnected and complex, so it’s really difficult to predict side effects and that’s why there is such a stringent, regulatory process during these clinical trials. Even though there is an active outbreak going on, we can’t just rush these things out to the market because we want to be sure that the drug can bring clinical relief first,” says Wrapp.
For now, washing hands regularly, wearing masks in public and social distancing remain the best way to prevent the spread of COVID-19. Nevertheless, we can still be optimistic about the research being done to biologically combat this pandemic. Thanks to the llama, a treatment that could help save countless lives may be just around the corner.
Content Experts
Daniel Wrapp is a graduate student at the University of Texas, Austin. He led this research and is interested in characterizing host-pathogen interactions through structural and biophysical techniques.
Dr. Xavier Saelens is a Belgian Scientist at the University of Ghent. His work includes finding a universal influenza vaccine and antibody research for COVID-19 at his own lab, VIB-UGent.
Sources
Discovery of Nanobodies. (2019, March 08). Retrieved August 31, 2020, from https://www.chromotek.com/technology/discovery-of-nanobodies/
Dong, J et al. (2020, May 22). Development of multi-specific humanized llama antibodies blocking SARS-CoV-2/ACE2 interaction with high affinity and avidity. Retrieved August 31, 2020, from https://www.tandfonline.com/doi/full/10.1080/22221751.2020.1768806
Fenz, K. (2020, June 12). ‘Llama magic’: How antibodies from llamas may lead to COVID-19 treatment. Retrieved August 31, 2020, from https://medicalxpress.com/news/2020-06-llama-magic-antibodies-llamas-covid-.html
Interview with Daniel Wrapp. Interview by Eeshan Khurana. August 7, 2020.
Interview with Xavier Saelens. Interview by Eeshan Khurana. August 10, 2020
Llama antibody engineered to block coronavirus. (2020, June 02). Retrieved August 31, 2020, from https://www.nih.gov/news-events/nih-research-matters/llama-antibody-engineered-block-coronavirus
Wrapp, D et al. (2020, May 05). Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies. Retrieved August 31, 2020, from https://www.sciencedirect.com/science/article/pii/S0092867420304943
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This article was written by Eeshan Khurana. Eeshan and the cSw student editing team would like to thank Michael Newman for serving as a mentor on this story. Michael is a Senior Media Relations Representative at Johns Hopkins Medicine. As always, before leaving a response to this article please view our Rules of Conduct. Thanks! -cSw Editorial Staff