According to scientists, monoclonal antibodies—the result of cloning cells that produce antibodies—might offer a solution to the increasing issue of antimicrobial resistance.
Researchers at the University of Cambridge have created a monoclonal antibody treatment using genetically modified mice, which may help ward off infections from Acinetobacter baumannii. This particular bacteria is linked with infections acquired in hospitals and is especially prevalent in Asia.
The bacteria A. baumannii can lead to severe respiratory illnesses and sepsis in those most at risk, particularly newborns with underdeveloped immune systems. The infection mostly spreads through contaminated objects, medical devices, and close contact with infected individuals. Recently, strains of this bacteria that are immune to nearly all antibiotics have become widespread.
Professor Stephen Baker from the Cambridge Institute of Therapeutic Immunology and Infectious Disease stated, “A. baumannii sticks very well to medical instruments, making it especially dangerous for those with compromised immune systems, resulting in severe pneumonia that may require ventilation. Sadly, patients can often get this infection through the ventilation equipment itself.”
“This bacteria naturally resists many treatments, and since it is now commonly found in hospitals, it has gained resistance to almost all available antibiotics. In some hospitals throughout Asia, where the outbreaks are most severe, no antibiotic is effective at all. Treating these infections has become incredibly challenging.”
A study published in Nature Communications reveals that the team produced monoclonal antibodies using transgenic mice—mice engineered to have a human-like immune response, generating human antibodies instead of mouse antibodies. The findings show that these antibodies were effective in preventing infections from clinical samples of A. baumannii.
Monoclonal antibodies are becoming increasingly common in medicine, often used to treat various conditions such as cancer (for instance, Herceptin for breast cancer) and autoimmune disorders (like Humira for rheumatoid arthritis, psoriasis, Crohn’s disease, and ulcerative colitis).
Typically, monoclonal antibodies are developed from the antibodies of individuals who have recovered from an infection or are engineered to specifically target certain antigens. For example, monoclonal antibodies that focus on the ‘spike protein’ of the SARS-CoV-2 virus were investigated as potential treatments for COVID-19.
However, the Cambridge team employed a different strategy. They exposed transgenic mice to the outer membrane of the A. baumannii bacteria to stimulate an immune response. The researchers isolated nearly 300 antibodies to identify the most effective in recognizing live bacteria, pinpointing the monoclonal antibody mAb1416 as the standout.
Professor Baker explained, “In our approach, we do not expose the mice to live bacteria; instead, we immunize them with various components and allow the immune system to determine which to create antibodies for. Since these mice have humanized immune systems, there’s no need for further modifications to make the antibodies suitable for humans.”
The team administered mAb1416 to the mice, and 24 hours later, they were exposed to A. baumannii sourced from a child in an intensive care unit with sepsis. It was observed that treated mice had significantly lower bacterial levels in their lungs compared to untreated mice after another 24 hours.
All isolates used for producing and testing the monoclonal antibodies were collected from patients in Ho Chi Minh City, Vietnam. However, the isolate used for testing mAb1416 was from a patient ten years later than the other samples. This is significant as it demonstrates that mAb1416 is effective against A. baumannii that could have changed over time.
Professor Baker remarked, “With this method, we can use any bacterial antigen or a combination of antigens rather than relying solely on patients who have recovered from specific infections, presuming they have developed suitable antibodies.”
Further research is required to understand how mAb1416 provides protection against infection, as this could help the team create even more effective treatments. Any potential new medications will need to undergo safety trials in animals before being tested in humans.
Professor Baker emphasized, “Monoclonal antibodies are known to be safe and effective, and the technology to produce them is available. We’ve figured out how to utilize them against bacteria. Besides the cost considerations, there’s no reason this couldn’t be available as a treatment within a few years. Considering the urgent challenge of antimicrobial resistance, this could become a significant new tool in our arsenal.”
This research received funding from the Bill & Melinda Gates Foundation, the UK Medical Research Council Newton Fund, the Viet Nam Ministry of Science and Technology, and Wellcome.
