Vilnius University (VU) Prof. Aurelija Žvirblienė, who heads the Immunology Department of the Life Sciences Center, together with her team, has created hundreds of unique antibodies directed against viral and bacterial proteins, recombinant cytokines, cell receptors, or allergens.
"Over more than twenty years, we have developed a wide variety of antibodies, some of which have been successfully commercialized by companies. These antibodies can be used in diagnostics and further scientific research," says the professor, whose department focuses on antibody development, engineering, and application.
Antibodies and macrophages – the “actors” of our immune system
Each of us has a huge variety of antibodies. Antibodies are proteins produced by B lymphocytes in our body. B lymphocytes are the only cells that can secrete antibodies, and this process occurs constantly in our body.
"When B lymphocytes are activated, they begin to secrete antibodies, which perform various functions. Perhaps the most well-understood function for everyone is the ability of antibodies to "neutralize" bacterial toxins or, when attached to a virus, prevent them from infecting our cells. Antibodies are constantly produced in our body and are a very important part of our immune system," the professor notes.
It is important to understand that antibodies bind specifically to the antigen that caused them.
"If we have had COVID-19, our bodies have developed antibodies that recognize the virus that caused the disease. But these antibodies will not help us protect ourselves from the flu or staph infection," the scientist emphasizes.
Antibodies are specific molecules that bind only to their target. It is this property that allows scientists to use antibodies to recognize certain substances.
"When conducting research in the laboratory, we create antibodies that are directed against a specific antigen. This allows us to tailor these antibodies to detect these antigens," the professor says.
The department headed by Prof. A. Žvirblienė also conducts fundamental research, which aims to clarify how our immune system works, how its components react to viral antigens, and what molecular mechanisms are activated.
"We focus most of our attention on the part of the immune system that responds very quickly to infection - innate immunity. One of the components of innate immunity is macrophages, which are very quickly able to detect a foreign pathogen and respond in one way or another. Often during infections we can feel various symptoms, such as fever and others, which may be a consequence of macrophage activation. So my colleagues and I, using cell models vitro "(in a test tube), we are trying to figure out the molecular mechanisms that occur when macrophages are activated," says the professor.
From immune response to hybridoma technology
Prof. A. Žvirblienė recalls that the interest in the topic of antibodies was particularly high during the COVID-19 pandemic. Many of us tried serological tests that could detect antibodies specific to the coronavirus, so scientists were asked what the difference was between IgG and IgM antibodies.
"B lymphocytes have the ability to produce antibodies of different classes at different activation periods. At the beginning of an infection, mainly IgM class antibodies are produced, which do not have many functions and only partially protect. Upon repeated exposure to an antigen, not only does the quality of the antibodies improve, their class changes, but their interaction with the target antigen also strengthens," says the scientist.
"For example, if we have an infection, we usually benefit most from IgG class antibodies, which activate various immune cells and carry out neutralization. Therefore, the aim is to produce IgG class antibodies after vaccination," the interviewee explains.
Antibodies are specialized and adapted to perform different functions. For example, IgA class antibodies are secreted in the intestinal or respiratory mucosa, which are adapted to act and neutralize microbes specifically in the mucous membranes.
"When developing vaccines, it must be ensured that the necessary class of antibodies is formed after vaccination, which will be able to stop the spread of the pathogen," says the professor.
Antibodies are formed naturally in our body. After infection or vaccination, each of us has different classes of antibodies. This is a natural result of the activation of our immune system. At the same time, monoclonal antibodies are being developed in laboratories. These antibodies are also being developed by Prof. A. Žvirblienė and her team.
"Back in 1975, a technology was developed that allows large-scale production of antibodies against a desired substance in the laboratory. This is what distinguishes this technology from the traditional method used previously, when antibodies were isolated from blood serum. Blood serum always contains a mixture of antibodies - they are formed against various proteins, viruses, and bacteria that we encounter in life. Hybridoma technology allows us to select clones of B lymphocytes (identical cells) that produce antibodies of a specific specificity that we need - monoclonal antibodies," says the scientist.
By fusing B lymphocytes with cancer cells, scientists can culture such cells vitro and obtain specific antibodies in large quantities.
"Such monoclonal antibodies can be used for various diagnostic methods and therapies. Often, monoclonal antibodies are obtained using B lymphocytes from animals, so they are not suitable for treatment and require additional manipulations to make them as similar as possible to human antibodies. Then they can be used to treat cancer or certain inflammatory diseases," says the professor.
Antibody catalog of VU scientists
Prof. A. Žvirblienė and her team have developed monoclonal antibodies against a variety of antigens, such as viral proteins, bacterial toxins, allergens, cytokines, and hormones.
"We can use these monoclonal antibodies as a very specific reagent for detecting those specific antigens, specific substances. We have a huge collection of these antibodies," the researcher says.
VU scientists also perform antibody engineering, for example, using genetic engineering methods to transform a mouse monoclonal antibody into a human antibody as similar as possible.
"Such antibodies mimic human antibodies and can be used as positive controls in the development of various diagnostic tests. Also, the "humanization" of antibodies is widely used in the development of therapeutic antibodies. But, of course, we, as a scientific laboratory, are not engaged in the development of such therapeutic antibodies. It would be really difficult to compete with large pharmaceutical companies that do this," says the professor.
The antibodies developed by Prof. A. Žvirblienė and colleagues can become a useful molecular tool for further scientific research, as they allow for the study of the structural properties of proteins.
"By creating antibodies that neutralize the biological action of a protein and determining which site on the protein that antibody is directed against, we can study the functional activity of that protein. Together with other methods, this helps to clarify the mechanism of action of the protein," the scientist explains.
Prof. A. Žvirblienė is pleased that the laboratory she leads is part of the European network of scientific laboratories developing antibodies, EuroMabNet.
"We joined this network only six years ago and are very happy to be involved in its activities and share good practices. We have important work ahead of us - in 2026 we will organize the international EuroMabNet conference in Vilnius," says the professor.
Antibodies – a way to treat diseases
When developing antibodies for therapy, it is crucial that they are as similar as possible to human antibodies. This is the only way to ensure that the therapeutic antibodies will perform their function and not cause adverse reactions.
"If we simply took mouse antibodies and used them for treatment, the human immune system would recognize them as foreign and they would cause various adverse reactions. Therefore, when developing therapeutic antibodies, their molecules must be identical or as similar as possible to human antibodies. This is the only way to ensure an effective immune response and not cause adverse reactions in the body," the interviewee notes.
Antibodies are used to treat some autoimmune diseases, such as rheumatoid arthritis. In this case, therapeutic antibodies neutralize a cytokine that causes inflammation.
"The body of a person with rheumatoid arthritis produces too much of a cytokine that causes inflammation. When antibodies are injected, they neutralize this cytokine, which can reduce the symptoms of the disease," says Prof. A. Žvirblienė.
Another important area of application of therapeutic antibodies is cancer treatment. One group of anti-cancer antibodies is designed to inhibit the formation of blood vessels (capillaries). Blocking the formation of these blood vessels can also inhibit the growth of cancer tumors. Another way to use antibodies in cancer treatment is to direct them against an antigen that is unique to cancer cells.
"A common problem is that healthy cells can also have such an antigen on their surface. In this case, those antibodies may be ineffective or activate our immune system to fight healthy cells, thus causing unwanted reactions. Therefore, developing therapeutic antibodies requires a very long verification process," says the researcher.
Patented antibodies and monetary challenges
Prof. A. Žvirblienė and her colleagues have even patented several antibodies. The scientist emphasizes that in order to patent a new antibody, it must not be described in any published articles and must be directed against a completely new target.
"One of our patented antibodies was against a fish allergen, which was first isolated in Lithuania from Lithuanian carp. This fish is not found in other countries, so this allergen is not present either. This antibody was truly unique and it was not very difficult to patent it," the scientist gives an example.
The professor acknowledges that one of the biggest challenges is the high cost of international patents and the long issuance time.
"Each correspondence with patent attorneys, discussing aspects of novelty, takes a really long time, and the patent application itself can cost tens of thousands of euros. Patent maintenance fees must be paid later, so before patenting, you always need to carefully consider whether this patented antibody will be able to be applied in practice and will have commercial benefits," she says.
The situation in the business world is different - most antibodies intended for therapy are patented.
"There's a lot of money involved in the pharmaceutical industry, and companies are interested in protecting their developed antibodies for twenty years and reducing competition. Later, drugs are developed based on these antibodies, which bring in really big profits," says the professor.
Prof. A. Žvirblienė notes that many of their antibodies have been commercialized by companies that include them in their catalogs.
"Those companies pay us licensing fees. This income is constant and very valuable to us, because the calendar of project calls is volatile, and getting funding for projects is sometimes not so easy. Contracts with companies are a great example of how antibodies created in the laboratory generate real income, and at the same time give us, scientists, a sense of satisfaction, because our knowledge and experience have been applied in practice," says the scientist.
