Antibody therapy could treat infections caused by a dangerous strain of bacteria that most antibiotics cannot kill. Although the treatment has not yet been tested in humans, it is effective in mice.
Methicillin resistant Staphylococcus aureus (MRSA) is one of the deadliest bacteria. It killed more than 100,000 people worldwide in 2019 and evolved to evade all but seven antibiotics.
“One of the challenges of treating [MRSA] is that the body is very good at escaping different immune responses,” explains Victor Torres at NYU Langone Health in New York. This includes the body’s deployment of proteins called antibodies, which identify and attack pathogens.
Torres and his team developed a treatment by introducing genetic mutations into a human antibody that attacks MRSA. They engineered small proteins called centyrines on the surface of the molecule – these prevent bacteria from punching holes in immune cells. The modified antibody targets 10 pathogenic mechanisms of MRSA.
To test its effectiveness, the researchers administered antibody infusions to 20 mice 4 hours after they were infected with MRSA. Half of the mice received infusions with the new antibody treatment while the other half received antibodies that were ineffective against the bacteria.
After three days, skin lesions in mice treated with modified antibodies were, on average, 95% smaller than those seen in the control group. They also had an average of 98% fewer bacteria in the infected tissues than the untreated animals, indicating that the treatment can eliminate MRSA infections that progress to other organ systems.
The team conducted a separate experiment on 54 mice with MRSA-induced kidney infections and found that antibody treatment boosted the effectiveness of vancomycin, one of the so-called “last resort” antibiotics. Mice on combination therapy had 99% fewer bacteria in kidney tissue than mice treated with vancomycin alone.
“Even if [this] product were to fail to meet efficacy criteria in human clinical trials, this is a significant step forward,” says Jim Cassat at Vanderbilt University Medical Center in Tennessee. Indeed, it offers a new model for the design of therapeutic antibodies, he says.
“Number of [effective] the antibiotics went down and down and down,” Torres says. “So the importance of this research is to provide a new option, or at least a new pathway by which we can generate new treatments to prevent death and infections.”