Introduction

Hens—female chickens—are domestic birds that we are all familiar with. Their meat and eggs provide much of the protein needed to prevent hunger all over the world. Beyond this traditional purpose, hens have another hidden treasure—a protein known as IgY. IgY is a type of antibody—an important component of the immune system. To understand IgY and appreciate its power, we will first delve into what antibodies are.

What Are Antibodies and Why Are They Important?

Antibodies are a special type of proteins found in the blood. They are part of the body’s immune system—its defense system against dangerous invaders like bacteria and viruses. Most antibodies are made from four proteins bound together. Two of the proteins are longer and are called heavy chains, while the other two shorter chains are called light chains. These four chains are linked to each other to form the three-dimensional structure of the antibody molecule, which resembles the letter Y (Figure 1).

Have you ever wondered why your parents take you to the doctor for immunizations (“shots”), even though you are healthy? Immunizations protect us from germs such as viruses that we may encounter in the future. Immunizations contain harmless components of the viruses, bacteria, or other germs. When we are immunized, these components “teach” the body to react in case we encounter the dangerous form of the germ in the future. An informed immune system is always on the lookout for alien substances that may harm us, and it is ready to produce antibodies to help our bodies fight off these invaders.

Antibodies Recognize Antigens

Antibodies recognize a tiny part of a germ, called an antigen, and they initiate a response by the rest of the immune system that will kill the germ. Antibodies are produced by cells of the immune system called B cells. B cells can “remember” an encounter with a germ and, if the body encounters the same germ again, the B cells will quickly start producing antibodies [1].

The ability of antibodies to recognize antigens comes from the tips of the “Y,” called the antigen-binding sites of the antibodies (Figure 1) [2]. All the antibodies produced by one B cell are the same, but they have different antigen-binding sites than the antibodies produced by any other B cell. This means that each B cell produces antibodies that can identify only one antigen. In the body, there are millions of B cells and thus millions of different kinds of antibodies. Chances are there is at least one antibody in the body that will recognize just about any type of dangerous invader that comes along. These antibodies include those generated against germs we encountered when were just babies.

Most Animals Have Antibodies

All vertebrates—including fishes, amphibians, reptiles, birds, and mammals—produce antibodies. Each vertebrate has slightly different types (called classes) of antibodies in its body (Figure 2). The names of antibody classes are shortened using the abbreviation Ig (for immunoglobulin, another word for antibody) followed by a letter of the alphabet. Mammals (including humans) have five classes of antibodies: IgA, IgD, IgE, IgG, and IgM. IgG is the main antibody released during the immune response in mammals. IgF and IgX are classes of antibodies found in amphibians, while IgZ is found in fishes [3]. In birds, the main antibody class is IgY. Both IgG and IgY have similar “Y”-shaped structures, but with some notable differences that make the IgY structure more stable than IgG.

Meet the Heroes: Production of Antibodies in Animals for Human Use

Using the principles of immunization discussed earlier, scientists can instruct the immune systems of many animals to produce antibodies against whichever antigens they choose. For example, a scientist can immunize an animal with a piece of a virus and that animal will generate antibodies against the virus. But the purpose of generating antibodies this way is not to use them to protect the immunized organism—it is to use them to protect another organism—humans.

Antibodies are generally found in the liquid part of the blood, which is called the serum. In birds, IgY can also be found in egg yolks. Any animal that produces antibodies could be used by scientists to produce antibodies for use in humans. However, imagine having to obtain the blood of a polar bear or a tiger shark! For practical reasons, only a handful of animals are used to generate the antibodies used in medicine: mice, rats, rabbits, goats, sheep, horses, and hens. Each of these organisms has its advantages and disadvantages. For example, rodents like rats and mice are easy to handle but do not have much blood; while bigger animals like sheep and horses are more difficult to handle, but larger amounts of blood can be taken from them.

Scientists worry about the pain animals might feel when their blood is drawn. Recently, there is a growing push from scientists and the public to protect research animals. A plan called the 3Rs has been developed, with the Rs being: Reduce the number of animals used, Refine experiments so that they cause the least possible suffering to animals, and Replace animals with other methods [for more information on improving animal welfare by reducing (Tremoleda, 2022), refining (Jirkof, 2022), and replacing (Hartung, 2022), see the linked Frontiers for Young Minds articles. Here is where hens save the day!].

Why Hens Are the Best

Like all birds, hens lay eggs. After hens encounter an antigen, their egg yolks naturally contain large amounts of IgY. A laying hen can produce over 300 eggs during her lifespan—that is a lot of antibodies! Obtaining antibodies from hen eggs helps scientists practice the 3Rs (Figure 3). First, since large amounts of IgY can be obtained from each egg, eggs can easily be used to Replace the blood of other research animals. Collecting 150 eggs from one hen saves more than 144 mice, so this Reduces the number of animals used in experiments. Finally, laying eggs is not as painful as having blood drawn, so the antibody-production process has been Refined to minimize animal suffering. Thus, the 3Rs are achieved—use of hens improves animal welfare in antibody-production research [4].

Uses of Hen IgY in Healthcare

IgY antibodies have many uses in human medicine, for both detection of diseases and disease treatment. In terms of detection, IgY has been used to detect and quantify cancers. Diseases caused by bacteria, such as meningitis or sepsis, can be detected using IgY [5]. IgY can also be used to detect harmful or illegal drugs in human urine. Finally, IgY has also been used to detect the virus that causes severe acute respiratory syndrome, a cousin of COVID-19 [6].

Regarding treatment, IgY has been used in the safe treatment of dental cavities and stomach ulcers [7]. When it comes to treating diseases, IgY has a major advantage over antibodies from mammals, because IgY is not broken down by the body as quickly as mammalian antibodies are. Scientists have also developed clever ways to further protect IgY from the harsh conditions of the gut. So, IgY is a very good drug for treating infections, especially infections of the gut and airways. Who knows—we may soon see a type of IgY that will be useful for treating COVID-19.

Summary

Antibodies are very important molecules, and our bodies produce them to protect us against infections. Antibodies generated in animals such as mice, rabbits, and hens can also be used in healthcare. Hens produce antibodies of a class known as IgY, and these antibodies can be isolated from hen eggs. Hen IgY has advantages over antibodies from other animals and it has been used to safely treat many human and animal diseases. In the future, more diseases will be treated with IgY, further improving human health while also promoting the welfare of laboratory animals.

Glossary

Antibody: ↑ A type of protein that helps the body fight foreign invaders.

Immune System: ↑ A group of cells, and the substances they produce, that together help the body stay healthy by fighting off germs like viruses and bacteria.

Immunization: ↑ The act of giving a person or animal a non-harmful component of an infectious organism to protect the person/animal from harmful infection with that organism in the future.

Antigen: ↑ A substance that can cause the body to produce antibodies. Examples of antigens are viral proteins and pollen from plants.

Antigen-Binding Site: ↑ If an antibody is seen as a lock, and the antigen as a key, the antigen-biding site would be the keyhole where the key fits.

Serum: ↑ The liquid part of the blood that surrounds the blood cells.

Acknowledgments

We thank Rao Wu for his excellent support in figure preparation, and thank Siran Zhang for her careful and thoughtful proof-reading.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.