Scientists claim that monoclonal antibodies, which are treatments derived from cloning cells that produce antibodies, might be a solution to the rising issue of antimicrobial resistance.
A research team from the University of Cambridge has created a monoclonal antibody medication using genetically modified mice, aimed at preventing infections caused by Acinetobacter baumannii. This particular bacterium is linked with infections acquired in hospitals, especially prevalent in Asia.
The A. baumannii bacteria can lead to severe respiratory illnesses and sepsis, particularly in at-risk individuals such as newborns, whose immune systems are still developing. The bacteria typically spread through contaminated surfaces, medical devices, and interpersonal contact. Recently, strains of this bacterium that resist nearly all available antibiotics have become increasingly common.
Professor Stephen Baker from the Cambridge Institute of Therapeutic Immunology and Infectious Disease pointed out that “A. baumannii adheres effectively to medical instruments; vulnerable individuals or those with underdeveloped immune systems may fall victim to infections that result in severe pneumonia needing ventilation. In many instances, patients can contract the infection from the very ventilation apparatus.”
“This bacterium naturally resists various antimicrobials, but its presence in hospitals has led it to gain resistance against almost all treatments we can employ. Many hospitals in Asia, where these infections are prevalent, have no antibiotics effective against them. They’ve turned into untreatable infections.”
In a study released today in Nature Communications, the researchers produced monoclonal antibodies using transgenic mice with human-like immune systems that produce human antibodies instead of mouse ones. They demonstrated that these monoclonal antibodies effectively prevented infections from A. baumannii strains derived from clinical specimens.
Monoclonal antibodies are an expanding area in medicine, frequently used to address conditions like cancer (e.g., Herceptin for certain breast cancers) and autoimmune disorders (e.g., Humira for rheumatoid arthritis, psoriasis, Crohn’s disease, and ulcerative colitis).
Typically, monoclonal antibodies are derived from the antibodies of patients who have recovered from an infection, or specifically engineered to target a certain antigen. For instance, antibodies aimed at the ‘spike protein’ of the SARS-CoV-2 coronavirus were tested for treating COVID-19.
However, the Cambridge researchers took a different approach by exposing transgenic mice to the outer membranes of A. baumannii, which prompted an immune response. They isolated nearly 300 various antibodies to see which was most effective against live bacteria, eventually identifying mAb1416 as the top candidate.
According to Professor Baker: “In this method, we’re not infecting the mice with live bacteria; instead, we immunize them with different elements, allowing the mouse’s immune system to determine the appropriate antibodies to develop. Since these mice have ‘humanized’ immune systems, we don’t need to modify the antibodies for human compatibility.”
The researchers treated mice with mAb1416 and then after 24 hours exposed them to A. baumannii samples from a child suffering from sepsis in an intensive care setting. They observed that the treated mice showed a notable decrease in the bacterial load in their lungs after another 24 hours, compared to untreated mice.
All samples used for producing and evaluating the monoclonal antibodies came from patients in Ho Chi Minh City, Vietnam; notably, the sample for testing mAb1416 was collected a decade later than the others. This detail is crucial as it demonstrates that mAb1416 remained effective against A. baumannii variants that may have developed throughout the years.
Professor Baker remarked: “This technique allows us to utilize any bacterial antigen or a mix of antigens, eliminating the need to wait for someone who has recovered from an infection and we hope has built the right immune response to extract their antibodies.”
Further research is essential to understand how mAb1416 protects against infections, which could lead to an even more effective treatment. Any potential new drug will require thorough safety trials in animals before entering human trials.
Professor Baker concluded: “We are aware that monoclonal antibodies are safe and effective, and the technology to produce them is in place. What we’ve accomplished is discovering how to use them against bacteria. Beyond the cost-effectiveness, there’s no reason this couldn’t evolve into a medicinal solution within a few years. Given the urgent challenge posed by antimicrobial resistance, this could potentially serve as a robust new strategy to fight back.”
The research was supported by the Bill & Melinda Gates Foundation, the UK Medical Research Council Newton Fund, the Ministry of Science and Technology of Vietnam, and Wellcome.
