Research Finds Monoclonal Antibodies May Help Combat Antimicrobial Resistance In Hospital-acquired Infections - Video

A team led by researchers at the University of Cambridge has developed a monoclonal antibody drug, using a technique involving genetically engineered mice, that may help prevent infection from Acinetobacter baumannii, a bacteria associated with hospital-acquired infections, which is particularly common in Asia.

Professor Stephen Baker from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the University of Cambridge said "A. baumannii is good at sticking to medical equipment, and if people are vulnerable or don't have a particularly well-developed immune system, they can succumb to this infection and get aggressive pneumonia requiring ventilation -- and in many cases, the patients can acquire the infection from the ventilation itself.

"The bacteria are naturally resistant to many antimicrobials, but as they're now found in hospitals, they've acquired resistance to almost everything we can use. In some hospitals in Asia, where the infections are most common, there isn't a single antibiotic that will work against them. They've become impossible to treat."

In a study published today in Nature Communications, the team produced monoclonal antibodies using transgenic mice -- mice that have been genetically-engineered to have a human-like immune system, producing human antibodies instead of mouse antibodies. They went on to show that these monoclonal antibodies were able prevent infection with A. baumannii derived from clinical samples.

Monoclonal antibodies are a growing area of medicine, commonly used to treat conditions including cancer (for example, Herceptin for treating some breast cancers) and autoimmune disease (for example, Humira for treating rheumatoid arthritis, psoriasis, Crohn's disease, and ulcerative colitis).

Usually, monoclonal antibodies are developed from the antibodies of patients who have recovered from an infection, or they are designed to recognise and target a particular antigen. For example, monoclonal antibodies targeting the 'spike protein' of the SARS-CoV-2 coronavirus were explored as a way of treating COVID-19.

In the approach taken by the Cambridge team, however, transgenic mice were exposed to the outer membrane of A. baumannii bacteria, triggering an immune response. The researchers then isolated almost 300 different antibodies and tested which of these was the most effective at recognising live bacteria, identifying the single monoclonal antibody mAb1416 as the best.

Reference: Stephen Baker, Aishwarya Krishna, Sophie Higham, Plamena Naydenova, Siobhan O’Leary, Josefin Bartholdson Scott, Katherine Harcourt, Sally Forrest, David Goulding, To Nguyen Thi Nguyen, Nguyen Duc Toan, Elizaveta Alekseeva, Qingqing Zhou, Ilaria Andreozzi, Barbara Sobotic, Hannah Craig, Vivian Wong, Nichola Forrest-Owen, Dana Moreno Sanchez, Claire Pearce, Leah Roberts, Simon Watson, Simon Clare, Mili Estee Torok, Gordon Dougan, Paul Kellam, John S. Tregoning, Stephen T. Reece. Exploiting human immune repertoire transgenic mice for protective monoclonal antibodies against antimicrobial resistant Acinetobacter baumannii. Nature Communications, 2024; 15 (1) DOI: 10.1038/s41467-024-52357-8