Abstract
Enterococcus faecium is a leading cause of nosocomial infections, particularly in immunocompromised patients. The rise of multidrug-resistant E. faecium, including Vancomycin-Resistant Enterococci (VRE), is a major concern. Vaccines are promising alternatives to antibiotics, but there is currently no vaccine available against enterococci. In a previous study, we identified six protein vaccine candidates associated with extracellular membrane vesicles (MVs) produced by nosocomial E. faecium. In this study, we immunized rabbits with two different VRE-derived MV preparations and characterized the resulting immune sera. Both anti-MV sera exhibited high immunoreactivity towards the homologous strain, three additional VRE strains, and eight different unrelated E. faecium strains representing different sequence types (STs). Additionally, we demonstrated that the two anti-MV sera were able to mediate opsonophagocytic killing of not only the homologous strain but also three unrelated heterologous VRE strains. Altogether, our results indicate that E. faecium MVs, regardless of the purification method for obtaining them, are promising vaccine candidates against multidrug-resistant E. faecium and suggest that these naturally occurring MVs can be used as a multi-antigen platform to elicit protective immune responses against enterococcal infections.