Periprosthetic joint infection occurs in 2%-4% of patients and is most often caused by Staphylococcus aureus.

These infections frequently require prolonged antibiotic courses and may fail because of antimicrobial resistance and the formation of bacterial biofilms on implants. Unresolved periprosthetic infections can lead to implant loosening, arthrodesis, and amputation. 

A preclinical study led by David Mooney at the Harvard University Wyss Institute for Biologically Inspired Engineering in Boston evaluated the ability of a biomaterial-based injectable scaffold system to elicit an adaptive immune response and mitigate S aureus orthopedic device infection in an established murine model.

This scaffold is injectable and biodegradable, composed of mesoporous silica rods, and contains aligned nanopores that can be exploited for the controlled delivery of granulocyte-macrophage colony-stimulating factor to recruit dendritic cells via chemotaxis.

To activate the dendritic cells that infiltrated the scaffold, demethylated cytosine-phosphate-guanine, a toll-like receptor 9 agonist, was added to the system as a vaccine adjuvant.

These scaffold vaccines increase cytokine production and antigen-specific cell-mediated immune and humoral responses. When loaded with a pool of antigens collected via engineered human opsonins, these scaffold vaccines decreased the bacterial burden of methicillin-susceptible and methicillin-resistant S aureus strains in a murine model of orthopedic device infection.

According to the authors “scaffold vaccination was about 100 times more effective in decreasing S aureus burden compared with prior published immunotherapy attempts in murine models of orthopedic device infection.”

Mooney noted that scaffold vaccination was well tolerated and generated Th1-associated immunity with increased antigen-specific cell-mediated and humoral responses. Compared with conventional bolus vaccination, scaffold vaccination decreased the bacterial burden in a murine model of orthopedic device infection.

The protective effect of scaffold vaccination was generalizable to different S aureus strains. 

The scaffold vaccine platform also mitigated infections with conventional monovalent protein-based antigens. Scaffold vaccination elicited a more robust immune response in mice than bolus vaccination.

“Outside infection, directing cell-mediated immune responses with scaffold vaccine technology may have broad implications for immunotherapy against cancer, autoimmune disease, and other health conditions,” the authors wrote.

This story was translated from MediQuality, part of the Medscape Professional Network.