Prof. Aurelija Žvirblienė, head of the Immunology Department at Vilnius University’s Life Sciences Center (LSC), together with her team, has developed hundreds of unique antibodies targeting viral and bacterial proteins, recombinant cytokines, cell receptors, and allergens.
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| Prof. Aurelija Žvirblienė with her team. Photo by Justinas Auškelis |
“Over more than twenty years, we have developed a great variety of antibodies, some of which have been successfully commercialized by companies. These antibodies can be applied in diagnostics and further scientific research,” says Prof. Aurelija Žvirblienė, whose department specializes in antibody development, engineering, and application.
Antibodies and Macrophages – Key Players in Our Immune System
Each of us has a wide array of different antibodies. Antibodies are proteins produced by B lymphocytes in our bodies. B lymphocytes are the only cells capable of secreting antibodies, and this process continuously takes place in the body.
“When B lymphocytes are activated, they begin to secrete antibodies that perform various functions. The most familiar function to most people is the ability of antibodies to 'neutralize' bacterial toxins or, by binding to a virus, prevent it from infecting our cells. Antibodies are constantly produced in our body and are a vital part of our immune system,” the professor notes.
Understanding that antibodies bind specifically to the antigen that triggered their production is essential.
“If we had COVID-19, our body developed antibodies that recognize the virus causing the disease. But those antibodies won’t help protect us from the flu or a staph infection,” the scientist emphasizes.
Antibodies are particular molecules that bind only to their target. This very property allows scientists to use antibodies to detect certain substances.
“In our laboratory research, we create antibodies directed against specific antigens. This enables us to use them to detect those antigens,” explains the professor.
Prof. Žvirblienė’s department also conducts fundamental research to understand how our immune system functions, how its components respond to viral antigens, and which molecular mechanisms are activated.
“We mainly focus on the part of the immune system that reacts quickly to infections – the innate immune system. One of its key components is macrophages, which can detect foreign pathogens and respond accordingly rapidly.
The symptoms we feel during infections, such as fever and others, can often result from macrophage activation. Together with colleagues, we use in vitro cell models to investigate the molecular mechanisms involved in macrophage activation,” says the professor.
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From Immune Response to Hybridoma Technology
Prof. Aurelija Žvirblienė recalls that interest in antibodies surged during the COVID-19 pandemic. Many people took serological tests to detect antibodies specific to the coronavirus, and researchers frequently received questions about the differences between IgG and IgM antibody classes.
"B lymphocytes can produce different classes of antibodies depending on the activation stage. At the beginning of an infection, IgM antibodies are mostly produced. These have limited functionality and offer only partial protection. Upon repeated exposure to the antigen, both the quality and class of antibodies improve, along with stronger interaction with the target antigen," explains the professor.
"For example, IgG class antibodies are usually the most beneficial during an infection. They activate various immune cells and neutralize pathogens. That’s why the goal after vaccination is to stimulate the production of IgG antibodies," she adds.
Antibodies are specialized molecules tailored to perform different functions. For instance, IgA antibodies are secreted in the gut or respiratory mucosa, where they help neutralize microbes in those specific environments.
"When developing vaccines, it’s essential to ensure that the right class of antibodies is produced, capable of preventing the pathogen's spread," says the professor.
Antibodies form naturally in our bodies. After infection or vaccination, every individual develops different antibody classes - a natural result of immune system activation. In contrast, monoclonal antibodies are created in laboratories - something Prof. Žvirblienė and her team actively work on.
"Back in 1975, a breakthrough technology was developed that made it possible to produce large quantities of specific antibodies in the lab. This approach differs from traditional methods where antibodies were extracted from blood serum, which always contains a mixture of antibodies generated against various proteins, viruses, and bacteria encountered throughout life. Hybridoma technology allows us to select B cell clones (identical cells) that produce antibodies with the desired specificity—monoclonal antibodies," she explains.
By fusing B lymphocytes with cancer cells, scientists can cultivate hybrid cells in vitro and produce specific antibodies in large amounts.
"These monoclonal antibodies can be used in various diagnostic methods and therapies. Often, they are generated using B lymphocytes from animals, making them initially unsuitable for human treatment. Additional modifications are then required to make them resemble human antibodies, after which they can be used to treat cancer or certain inflammatory diseases," says the professor.
The Antibody Catalog of VU Scientists
Prof. Žvirblienė’s team has developed monoclonal antibodies against various antigens, such as viral proteins, bacterial toxins, allergens, cytokines, and hormones.
"We can use these monoclonal antibodies as highly specific reagents for detecting those exact antigens. We have an extensive collection of such antibodies," she says.
VU scientists also perform antibody engineering - for example, converting mouse monoclonal antibodies into human-like antibodies using genetic engineering methods.
"These humanized antibodies can serve as positive controls in the development of diagnostic tests. Humanization is also widely applied in the development of therapeutic antibodies. Of course, as an academic lab, we don’t develop therapeutic antibodies ourselves - it would be difficult to compete with large pharmaceutical companies," she notes.
Antibodies developed by Prof. Žvirblienė’s team can serve as valuable molecular tools in future research by helping scientists explore the structural features of proteins.
"When we develop antibodies that neutralize a protein’s biological function and identify the binding site, we can study the protein’s functional activity. Alongside other methods, this helps us uncover the mechanisms of protein action," the researcher explains.
She is also proud that her lab is part of the European Antibody-Producing Laboratory Network, EuroMabNet.
"We joined the network only six years ago and are happy to be part of it, sharing best practices. We’re also honored to host the international EuroMabNet conference in Vilnius in 2026," says the professor.
Antibodies – A Tool for Disease Treatment
When developing therapeutic antibodies, it is crucial that they closely resemble human antibodies to ensure efficacy and avoid adverse immune reactions.
"If we were to use unmodified mouse antibodies for treatment, the human immune system would recognize them as foreign and cause unwanted reactions. That’s why therapeutic antibodies must be either identical or very similar to human antibodies - to ensure they function properly and do not cause side effects," she explains.
Antibodies are already used to treat autoimmune diseases like rheumatoid arthritis, where they neutralize cytokines responsible for inflammation.
"In patients with rheumatoid arthritis, the body produces excessive amounts of inflammatory cytokines. When antibodies are administered, they neutralize the cytokine and reduce disease symptoms," says Professor Žvirblienė.
Another key application is cancer therapy. One group of therapeutic antibodies aims to inhibit blood vessel formation (angiogenesis), thus preventing tumor growth. Another strategy is to target antigens found only on cancer cells.
"A common challenge is that healthy cells may also have these antigens, making the antibodies ineffective or even harmful by triggering immune attacks against normal cells. That’s why developing therapeutic antibodies requires a long and careful validation process," she explains.
Patented Antibodies and Financial Challenges
Professor Žvirblienė and her colleagues hold several patents for antibodies. She emphasizes that for an antibody to be patented, it must not be described in any publication and must target a completely novel antigen.
"One of our patented antibodies targets a fish allergen that we isolated from Lithuanian carp - something unique to our region. Other countries don’t have this species, so they don’t have this allergen. This antibody was truly unique and not difficult to patent," she illustrates.
She admits that one of the most significant challenges is the high cost of international patents and the lengthy approval process.
"Every communication with patent attorneys and the discussions around novelty take time. A single patent application can cost tens of thousands of euros. Then you must pay maintenance fees. That’s why before applying for a patent, we carefully evaluate whether it has practical application and commercial value," she explains.
In the business world, the situation is different - most therapeutic antibodies are patented.
"There’s a lot of money in the pharmaceutical industry. Companies want to protect their antibodies for 20 years to reduce competition. These patented antibodies are then used to develop drugs that bring in significant profits," the professor explains.
Professor Žvirblienė adds that many of their antibodies have already been commercialized through licensing agreements with companies that include them in their product catalogs.
"These companies pay us license fees. That revenue is extremely important to us because research funding can be unpredictable. These agreements are a great example of how antibodies developed in the lab generate real income and bring us, as scientists, a sense of satisfaction that our knowledge has been applied in practice," she concludes.