Biology subjects

SADONES, O.

Publications and source records attributed to SADONES, O..

2 recordsLinked to original sources

bioRxiv2025

Identification of cross-reactive vaccine antigen candidates in Gram-positive ESKAPE pathogens through subtractive proteome analysis using opsonic sera

The Gram-positive pathogens of the ESKAPE group, Enterococcus faecium, and Staphylococcus aureus, are well-known to pose a serious risk to human health because of their high virulence and numerous drug resistances, making them a real concern in healthcare settings worldwide. To narrow down the list of previously identified promising protein vaccine candidates, a combination of several antigen discovery approaches was performed, in particular a "false positive analysis" of peptides generated by trypsin shaving with a subtractive proteome analysis. The final list of nine potential antigens included AdcAau, a protein performing the same function as AdcAfm, an already discovered antigen in enterococci. Bioinformatic analyses revealed that AdcAau and AdcAfm share a sequence identity of 41.2% and that the conserved regions had a high antigenicity. AdcAau was selected for further investigation and the results reported in this manuscript demonstrate the opsonic properties of AdcAau-specific antibodies against the S. aureus strain MW2, as well as their cross-binding and cross-opsonic activity against several S. aureus, E. faecium, and E. faecalis strains. This study suggests that further investigation of cross-reactive activities is a valuable tool for discovering new antigens that cover more than one clinically relevant pathogen.

immunology↗

bioRxiv2025

A self-assembling cross-protective antigen against multiple Gram-positive nosocomial pathogens

ESKAPE pathogens are responsible for complicated nosocomial infections worldwide and are usually resistant to commonly used antibiotics in clinical settings. Among these bacteria, vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus are the two most important Gram-positive pathogens for which alternative treatments and preventions are urgently needed. We previously designed a multi-presenting antigen, embedding the main epitope displayed by the AdcA protein of E. faecium, that conferred protection against different Gram- positive pathogens both in passive and active immunization models. Here, we developed a new presentation strategy for this epitope, the EH-motif, based on a self-assembling peptide. Self- assembling peptides have been promising in the fields of material sciences, nanoscience, and medicine and have also potential in vaccine development, as they allow multiple presentations of the epitope and provide an ideal size for production and application. We show that this multi- presenting peptide, here Q11-EH, forms stable fibers of nanometric size. We also demonstrate that antibodies raised against Q11-EH mediate the opsonic killing of a wide-spectrum of Gram-positive pathogens, including E. faecium, S. aureus, and E. faecalis. Our data indicate that multiple presentation strategies are a potent tool for vaccine antigen improvement and point to Q11-EH as a promising antigen for the development of novel cross-protective vaccines.

immunology↗