A groundbreaking vaccine strategy has emerged as a potential game-changer for patients with implanted medical devices, offering a promising solution to the persistent challenge of device infections.
For individuals with orthopedic joint replacements, pacemakers, or artificial heart valves, the risk of bacterial infections is a serious concern. These infections can lead to a cascade of complications, including the need for revision surgeries, prolonged antibiotic treatments, and, in the worst cases, amputation. The spread of infection within the body can even prove fatal.
Dr. Alexander Tatara, an Assistant Professor at The University of Texas Southwestern Medical Center, highlights the urgency of the situation: "In the U.S. alone, orthopedic surgeons perform a significant number of knee and hip replacements annually, and a small percentage of these devices become infected. These numbers underscore the critical need for effective preventive measures."
Researchers have long explored the potential of vaccines to protect against Staphylococcus aureus, the leading cause of orthopedic device infections. However, despite numerous efforts and large-scale clinical trials, an effective vaccine has remained elusive.
But here's where it gets controversial... A team of clinical researchers and bioengineers from the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard's John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a novel vaccine strategy that could revolutionize the prevention of device infections.
Their innovative approach involves the use of slowly biodegradable, injectable biomaterial scaffold vaccines. These vaccines are designed to attract and stimulate immune cells while presenting specific antigens from Staphylococcus aureus. When tested on a mouse model of orthopedic device infection, the vaccines triggered a beneficial immune response, reducing bacterial burden up to 100 times more effectively than conventional control vaccines.
And this is the part most people miss... The biomaterial vaccines not only protected against antibiotic-sensitive Staphylococcus aureus (MSSA) but also showed promise in guarding against antibiotic-resistant strains (MRSA). This opens up the possibility of developing off-the-shelf vaccines for broad use in orthopedic surgeries.
The study, led by Wyss Institute Founding Core Faculty member David Mooney, Ph.D., builds on previous work in the field of biomaterials-based vaccines. Mooney's team has successfully applied this approach to combat cancer and prevent sepsis and septic shock in animal models.
In this study, the researchers observed immune responses involving specific T cell populations, which may have been lacking in patients vaccinated with conventional vaccines in clinical trials. Additionally, the biomaterial vaccines induced Staphylococcus aureus-specific antibody responses, similar to those produced by soluble vaccine formulations.
David Mooney emphasizes the potential impact of their approach: "In combination with optimized antigen collections derived from Staphylococcus aureus species, our method could lead to novel biomaterials-based vaccines with the power to save lives and improve health outcomes globally."
The biomaterial vaccines provide a molecular training ground for dendritic cells (DCs), which act as central coordinators of the immune system, orchestrating a complex T cell response against pathogens in nearby lymph nodes. By incorporating immunogenic antigen components from disrupted bacteria using the Wyss Institute's FcMBL technology, the vaccines specifically program DCs to target infectious Staphylococcus aureus bacteria.
In mice vaccinated with the biomaterial vaccine and challenged with pathogenic Staphylococcus aureus bacteria, the strategy significantly reduced the overall bacterial burden compared to soluble control vaccines containing the same molecular components. The sustained and highly concerted engagement of the immune system by the biomaterial vaccines is believed to activate distinct types of T helper cells, which secrete protective cytokine molecules.
The team further validated their findings in a mouse model of actual orthopedic device infection. Animals vaccinated with the biomaterial vaccine showed a 100-fold stronger suppression of bacterial growth on implanted devices compared to soluble vaccine formulations.
Additionally, the researchers found that a biomaterial vaccine fabricated with antigens from methicillin-sensitive Staphylococcus aureus (MSSA) strains could also protect against later infection from methicillin-resistant (MRSA) strains, a significant concern in hospital settings.
Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS, Donald Ingber, comments on the study's implications: "This elegant and effective solution by Dave Mooney and his team has the potential to prevent infections in patients receiving joint replacements. Beyond orthopedic implants, it could serve as a versatile safeguard for various devices dwelling in the human body for extended periods, addressing similar infection-related challenges."
The study was authored by Shanda Lightbown, Shawn Kang, Wei-Hung Jung, Hamza Ijaz, Jean Lee, and Sandra Nelson, and supported by awards from the National Institutes of Health, Harvard Catalyst, and financial contributions from the Wyss Institute and Harvard University with its affiliated academic healthcare centers.
Reference:
Tatara, A. M., et al. (2025). Scaffold vaccination for prevention of orthopedic device infection. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2409562122
