Animals all over are helping scientists make antibodies to help fight human disease. Yes, some of them are cute.
A llama named Winter recently made headlines when scientists announced her small-but-mighty antibodies could fight the novel coronavirus. Think of it: A llama could save us from Covid-19.
Scientists have looked at “unusual” animal antibodies — including those of camelids, the family to which llamas belong — for decades to see how they might be harnessed for human treatments. In fact, the antibodies of horses, chickens, and even sharks could fight other, non-Covid-19 human afflictions.
In working with Winter, Xavier Saelens, PhD, a molecular virologist at Ghent University in Belgium, followed in the footsteps of other Belgian scientists who, in 1993, published their discoveries on llamas’ antibodies: Unlike human antibodies, which are made of both heavy and light chains of connected proteins, llamas can create antibodies that are composed of only heavy chains, making them smaller and nimbler, better able to bind to various pathogens. In cell tests, the llama antibodies neutralized the virus that causes Covid-19, and researchers are moving toward clinical human trials for a drug that uses the llama-derived antibodies by the end of this year.
Thanks in part to their size, and the accompanying higher volume of blood, horses produce large quantities of antibodies that have demonstrated efficacy against some infectious diseases.
Dozens of other animal antibody-derived treatments, for diseases ranging from lupus to rheumatoid arthritis and psoriasis, are currently under development or in clinical trials. Last year, the U.S. Food and Drug Administration approved Cablivi, a treatment derived from both llama and camel antibodies for a rare blood disorder called acquired thrombocytopenic purpura.
Here’s how the animal antibody research works: Animals are used as agents to create the type of antibodies scientists might want. For example, injecting an animal with a protein from human cancer will cause the animal’s immune system to generate antibodies that specifically target that cancer, says James A. Duty, PhD, a microbiologist who works in the Center for Therapeutic Antibody Development at Icahn School of Medicine at Mount Sinai. (While animals are injected with human diseases in order to produce antibodies, the doses are so mild, scientists say, that they don’t get sick.) Animal antibody research has long used mice and rabbits. But some scientists have moved beyond these critters and onto more unconventional animals in search of unique antibody properties that could better help fight disease or offer production benefits.
Thanks in part to their size, and the accompanying higher volume of blood, horses produce large quantities of antibodies that have demonstrated efficacy against some infectious diseases, including Ebola and H5N1 influenza virus, says Xi Song, PhD, a senior research scientist at Creative Biolabs. Horses are also easy to work with, he says.
Chickens are more apt to produce high-avidity antibodies, or antibodies that strongly bind to antigens, when compared to mammals — a very desirable quality, says Fawzi Al-Razem, PhD, a biochemist and dean of the College of Applied Sciences at Palestine Polytechnic University.
“The procedures we perform are no more painful or harmful than us getting our yearly flu jab or a routine blood test.”
Antibodies from chickens can also be taken from their eggs. “In one month, a single chicken can produce more than 10 times the number of antibodies that can be generated from a rabbit,” says Al-Razem. Those egg antibodies are available after just 25 days. That’s about a week sooner than it takes most other animal systems to produce high-avidity antibodies, Al-Razem explains.
Sharks’ antibodies are smaller than our antibodies — in fact, they’re even smaller than camelids’ antibodies — and researchers believe their diminutive size could fight viruses that can hide from immune destruction, such as Ebola, or be used in cancer treatments, says Helen Dooley, an immunologist at the University of Maryland who has worked with shark antibodies for more than 20 years. To study their antibodies, Dooley immunizes an aquarium’s nurse sharks with a killed virus or human cancer target, then returns to their tanks a few weeks later to collect small blood samples from their tails. (The sharks are, as one might expect, sedated for the process. But “the procedures we perform are no more painful or harmful than us getting our yearly flu jab or a routine blood test,” Dooley explains. The less aggressive, land-based animals don’t need to be sedated, and the injection and blood sampling are equally noninvasive, scientists say.)
Similarly, lampreys could hold appeal in antibody treatments. Max Cooper, MD, an immunologist at Emory Vaccine Center, has worked with the jawless fish for 20 years. He finds their antibodies to be “small and tough, and we think they can be used for a number of biological uses,” he says.
Whatever the animal, their antibodies must go through a process called humanization before they can be used in human treatments, says Duty. Humanization, which modifies the antibodies to make them more similar to human antibodies, allows the antibodies to retain their unique disease-fighting attributes while manipulating them so that the human body won’t reject them as foreign or something that it needs to fight. So rest easy: If one day you find yourself receiving a treatment derived from a shark, you won’t get ill — or grow fins. “The FDA will not let an antibody go forward without some measurable amount of humanization,” Duty says.