Enterococcal Membrane Vesicles as Vaccine Candidates

Abstract

<i>Enterococcus faecium</i> is a leading cause of nosocomial infections, particularly in immunocompromised patients. The rise of multidrug-resistant <i>E. faecium</i>, 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 <i>E. faecium</i>. 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 <i>E. faecium</i> 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 <i>E. faecium</i> MVs, regardless of the purification method for obtaining them, are promising vaccine candidates against multidrug-resistant <i>E. faecium</i> and suggest that these naturally occurring MVs can be used as a multi-antigen platform to elicit protective immune responses against enterococcal infections.