For years, medical investigators have tried and failed to develop vaccines for the deadly superbug methicillin-resistant Staphylococcus aureus (MRSA). But a new study at Cedars-Sinai shows how the staph cells evade the body’s immune system, offering a clearer picture of how a successful vaccine might work.

MRSA is one of the highest antibiotic-resistant threats in the U.S., accounting for more than 11,000 deaths per year, according to the Centers for Disease Control and Prevention. It is a particular problem for hospitalized patients whose immune systems could be weakened by illness.

“Widespread MRSA infections have prompted routine use of what were once last-line antibiotics, and this is worsening the antibiotic resistance problem,” says pediatric infectious diseases physician George Liu, MD, PhD, co-lead author of the study.

When exposed to illness-causing bacteria, the body typically fights them off and then “memorizes” the effective response for future use. But some may suffer from repeated staph infections without ever developing a robust protective immune response.

The study, using animal models, clarifies that staph bacteria contain an enzyme that prevents the cell wall from degrading, shielding it from detection by the body. Staph tricks the immune system such that T cells—white blood cells that fight infection—fail in their memorization task, opening the door to reinfection.

When scientists removed the protective enzyme from staph cell walls, the infection was detected, sparking a robust immune response that protected against reinfection.

While most attempts to create a staph vaccine have focused on stimulating antibodies, this study suggests that harnessing the body’s T cells could be a more successful path.