An antibody therapy could treat infections caused by a dangerous strain of bacteria that most antibiotics can’t kill. While the treatment hasn’t been tested in humans yet, 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 has evolved to evade all but seven antibiotics.
“One of the challenges in treating [MRSA] is that the organism is very good at escaping different immune responses,” says Victor Torres at NYU Langone Health in New York. This includes the body’s deployment of proteins known as antibodies, which identify and attack pathogens.
Torres and his team developed a treatment by introducing genetic mutations to a human antibody that attacks MRSA. They engineered small proteins called centyrins onto the molecule’s surface – these prevent bacteria from drilling holes into immune cells. The engineered antibody targets 10 disease-causing mechanisms of MRSA.
To test its efficacy, the researchers gave antibody infusions to 20 mice 4 hours after they were infected with MRSA. Half the mice received infusions with the new antibody treatment while the other half received antibodies ineffective against the bacteria.
After three days, skin lesions in the mice treated with engineered antibodies were, on average, 95 per cent smaller than those seen in the control group. They also had an average of 98 per cent fewer bacteria in infected tissues than untreated animals, indicating the treatment can clear MRSA infections that progress to other organ systems.
The team conducted a separate experiment in 54 mice with MRSA-induced kidney infections and found that the antibody treatment boosted the efficacy of vancomycin, one of the so-called “last resort” antibiotics. Mice on the combination therapy had 99 per cent less bacteria in kidney tissue than mice treated with vancomycin alone.
“Even if [this] product were to fail to reach efficacy endpoints in human clinical trials, it’s a significant step forward,” says Jim Cassat at Vanderbilt University Medical Center in Tennessee. That is because it offers a new blueprint for designing antibody therapeutics, he says.
“The number of [effective] antibiotics have been shrinking and shrinking and shrinking,” says Torres. “So, the importance of this research is to provide a new option, or at least a new pathway whereby we can generate new treatments to prevent death and infections.”