Researchers Seek Vaccine Against Bone Infection
Total joint replacement brings renewed mobility and better quality of life to approximately 1 million Americans each year, and as the population ages, the number of procedures is expected to reach 4 million by 2030. A group of UR Medicine physicians and researchers is working to reduce the risk of an uncommon but potentially serious side effect of this surgery: bone infection, known as osteomyelitis.
Removing a non-functioning joint to insert an artificial one can create an opportunity for infection-causing bacteria to enter bone. Osteomyelitis can be successfully treated, but it usually requires surgery and strong antibiotics. UR Medicine researchers are exploring ways to prevent it altogether – perhaps by developing a vaccine that patients receive before their joint surgery.
Before developing such a vaccine, the UR Medicine team needed to better understand the causes of bone infection and how the body’s immune system reacts to bacteria that can trigger it. We know that about half of bone infections in joint replacement surgery are caused by methicillin-resistant Staphylococcus aureus (MRSA) strains that are a particular worry in prosthetic joint infections – methicillin is the antibiotic often used to treat staph infection; strains of staph that are resistant to the drug are more difficult to treat). Since S. aureus exists everywhere, another challenge is that all people have a background immune response against this bacteria prior to infection. What we lack is a way to quickly identify whether the patient’s immune response is protective, or if the S. aureus has trick the patient’s immune system into making a non-protective antibody response that will render them susceptible to sepsis and death follow osteomyelitis.
UR Medicine researchers conducted research to improve early diagnosis of staph in bone infection patients. Their discoveries earned them the 2015 CORR® ORS Richard A. Brand Award for Outstanding Orthopaedic Research.
Kohei Nishitani, M.D, Ph.D.; Christopher A. Beck, Ph.D.; Alexander F. Rosenberg, Ph.D.; Stephen L. Kates, M.D.;Edward M. Schwarz, Ph.D., and John L. Daiss, Ph.D. authored the award-winning study, A Multiplex Assay of Host Immunity against S. aureus for Osteomyelitis Patients. Because early diagnosis would support more timely treatment and better patient outcomes, they developed a blood test to detect staph-related antigens (an antigen is part of a pathogen that trigger’s the body’s immune system to produce antibodies against it).
After studying blood samples from bone-infection patients and a control group of patients without infection, the team discovered that just four antigens triggered over 65 percent of the measurable staph antibodies in the patients they followed. When researchers considered 14 known staph antigens together, it gave them a very early, strong predictor of the presence of staph. Most importantly, the team discovered that a robust antibody response against the S. aureus antigens IsdA and IsdB is strongly associated with sepsis and death of osteomyelitis patients.
The ability to diagnose staph using a blood test means physicians can proactively screen for infection, identify it much earlier and treat it more quickly. Researchers’ findings about how the immune system fights staph infection will be useful as they develop a vaccine. In the future, millions of patients who need a new joint will have a vaccine to take before their procedure, and one less thing – bone infection – to worry about after.