A rationally designed antigen elicits protective antibodies against multiple nosocomial Gram-positive pathogens.

Autor: Kramarska E; Institute of Biostructures and Bioimaging, Italian Research Council (CNR), Naples, Italy., Toumi E; CNRS, INSERM, Institut Necker-Enfants Malades, U1151-Equipe 11, Faculté de Médecine, University of Paris City, Paris, France., Squeglia F; Institute of Biostructures and Bioimaging, Italian Research Council (CNR), Naples, Italy., Laverde D; Division of Paediatric Infectious Disease, Hauner Children's Hospital LMU, LMU, Munich, Germany., Napolitano V; Institute of Biostructures and Bioimaging, Italian Research Council (CNR), Naples, Italy., Frapy E; CNRS, INSERM, Institut Necker-Enfants Malades, U1151-Equipe 11, Faculté de Médecine, University of Paris City, Paris, France., Autiero I; Institute of Biostructures and Bioimaging, Italian Research Council (CNR), Naples, Italy., Sadones O; Division of Paediatric Infectious Disease, Hauner Children's Hospital LMU, LMU, Munich, Germany., Huebner J; Division of Paediatric Infectious Disease, Hauner Children's Hospital LMU, LMU, Munich, Germany., Skurnik D; CNRS, INSERM, Institut Necker-Enfants Malades, U1151-Equipe 11, Faculté de Médecine, University of Paris City, Paris, France. david.skurnik@inserm.fr.; Department of Clinical Microbiology, Fédération Hospitalo-Universitaire Prématurité (FHU PREMA), Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, University of Paris City, Paris, France. david.skurnik@inserm.fr.; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. david.skurnik@inserm.fr., Romero-Saavedra F; Division of Paediatric Infectious Disease, Hauner Children's Hospital LMU, LMU, Munich, Germany. felipe.romero@med.uni-muenchen.de., Berisio R; Institute of Biostructures and Bioimaging, Italian Research Council (CNR), Naples, Italy. rita.berisio@cnr.it.
Jazyk: angličtina
Zdroj: NPJ vaccines [NPJ Vaccines] 2024 Aug 18; Vol. 9 (1), pp. 151. Date of Electronic Publication: 2024 Aug 18.
DOI: 10.1038/s41541-024-00940-x
Abstrakt: ESKAPE pathogens are responsible for complicated nosocomial infections worldwide and are often resistant to commonly used antibiotics in clinical settings. Among ESKAPE, vancomycin-resistant Enterococcus faecium (VREfm) and methicillin-resistant Staphylococcus aureus (MRSA) are two important Gram-positive pathogens for which non-antibiotic alternatives are urgently needed. We previously showed that the lipoprotein AdcA of E. faecium elicits opsonic and protective antibodies against E. faecium and E. faecalis. Prompted by our observation, reported here, that AdcA also elicits opsonic antibodies against MRSA and other clinically relevant Gram-positive pathogens, we identified the dominant epitope responsible for AdcA cross-reactive activity and designed a hyper-thermostable and multi-presenting antigen, Sc(EH) 3 . We demonstrate that antibodies raised against Sc(EH) 3 mediate opsonic killing of a wide-spectrum of Gram-positive pathogens, including VREfm and MRSA, and confer protection both in passive and active immunisation models. Our data indicate that Sc(EH) 3 is a promising antigen for the development of vaccines against different Gram-positive pathogens.
(© 2024. The Author(s).)
Databáze: MEDLINE
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