The characterization of Klebsiella pneumoniae associated with neonatal sepsis in low- and middle-income countries to inform vaccine design
Abstract Klebsiella pneumoniae is the leading cause of neonatal sepsis, strongly associated to antimicrobial resistance, with no vaccine available. K-antigens (KAg) have been identified as potential targets, but their diversity makes vaccine development challenging. Alternatively, the use of subcaps...
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Nature Portfolio
2025-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08258-7 |
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| author | Francesca Nonne Mariagrazia Molfetta Gianina Florentina Belciug Martina Carducci Virginia Cianchi Casey Zakroff Salvatore Durante Caroline Zellmer Stephen Baker Thomas D. Stanton Kathryn E. Holt Kelly Wyres Neil Ravenscroft Gianmarco Gasperini Omar Rossi Carlo Giannelli Francesco Berlanda Scorza Francesca Micoli |
| author_facet | Francesca Nonne Mariagrazia Molfetta Gianina Florentina Belciug Martina Carducci Virginia Cianchi Casey Zakroff Salvatore Durante Caroline Zellmer Stephen Baker Thomas D. Stanton Kathryn E. Holt Kelly Wyres Neil Ravenscroft Gianmarco Gasperini Omar Rossi Carlo Giannelli Francesco Berlanda Scorza Francesca Micoli |
| author_sort | Francesca Nonne |
| collection | DOAJ |
| description | Abstract Klebsiella pneumoniae is the leading cause of neonatal sepsis, strongly associated to antimicrobial resistance, with no vaccine available. K-antigens (KAg) have been identified as potential targets, but their diversity makes vaccine development challenging. Alternatively, the use of subcapsular O-antigens (OAg) raises questions about antibodies accessibility. We characterized clinical isolates from the BARNARDS study, designed to identify the burden of neonatal sepsis in low-middle income countries. Genomic prediction was verified through structural analysis of polysaccharides. Antibodies generated against common KAg and OAg bound all homologous organisms, regardless of specific polysaccharide structural features. Interestingly, anti-KAg antibodies exhibited bactericidal activity against a comparable number of isolates as anti-OAg antibodies. There was no association between polysaccharide characteristics and K. pneumoniae susceptibility to killing. Antibody cross-reactivity among different KAg was observed, together with extensive cross-reactivity among OAg antibodies. This study aids in defining an optimal vaccine composition to prevent neonatal sepsis caused by K. pneumoniae. |
| format | Article |
| id | doaj-art-8c239b6d9b4f48d99093f75a217cc271 |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-8c239b6d9b4f48d99093f75a217cc2712025-08-20T02:40:15ZengNature PortfolioCommunications Biology2399-36422025-06-018111210.1038/s42003-025-08258-7The characterization of Klebsiella pneumoniae associated with neonatal sepsis in low- and middle-income countries to inform vaccine designFrancesca Nonne0Mariagrazia Molfetta1Gianina Florentina Belciug2Martina Carducci3Virginia Cianchi4Casey Zakroff5Salvatore Durante6Caroline Zellmer7Stephen Baker8Thomas D. Stanton9Kathryn E. Holt10Kelly Wyres11Neil Ravenscroft12Gianmarco Gasperini13Omar Rossi14Carlo Giannelli15Francesco Berlanda Scorza16Francesca Micoli17GSK Vaccines Institute for Global Health (GVGH)GSK Vaccines Institute for Global Health (GVGH)GSK Vaccines Institute for Global Health (GVGH)GSK Vaccines Institute for Global Health (GVGH)Department of Biomedical Sciences, Humanitas UniversityGSKGSKThe Department of Medicine, University of CambridgeA*STAR Infectious Diseases Labs (A*STAR IDL), Agency for Science, Technology and Research (A*STAR)Department of Infectious Diseases, School of Translational Medicine, Monash UniversityDepartment of Infectious Diseases, School of Translational Medicine, Monash UniversityDepartment of Infectious Diseases, School of Translational Medicine, Monash UniversityDepartment of Chemistry, University of Cape TownGSKGSK Vaccines Institute for Global Health (GVGH)GSK Vaccines Institute for Global Health (GVGH)GSK Vaccines Institute for Global Health (GVGH)GSK Vaccines Institute for Global Health (GVGH)Abstract Klebsiella pneumoniae is the leading cause of neonatal sepsis, strongly associated to antimicrobial resistance, with no vaccine available. K-antigens (KAg) have been identified as potential targets, but their diversity makes vaccine development challenging. Alternatively, the use of subcapsular O-antigens (OAg) raises questions about antibodies accessibility. We characterized clinical isolates from the BARNARDS study, designed to identify the burden of neonatal sepsis in low-middle income countries. Genomic prediction was verified through structural analysis of polysaccharides. Antibodies generated against common KAg and OAg bound all homologous organisms, regardless of specific polysaccharide structural features. Interestingly, anti-KAg antibodies exhibited bactericidal activity against a comparable number of isolates as anti-OAg antibodies. There was no association between polysaccharide characteristics and K. pneumoniae susceptibility to killing. Antibody cross-reactivity among different KAg was observed, together with extensive cross-reactivity among OAg antibodies. This study aids in defining an optimal vaccine composition to prevent neonatal sepsis caused by K. pneumoniae.https://doi.org/10.1038/s42003-025-08258-7 |
| spellingShingle | Francesca Nonne Mariagrazia Molfetta Gianina Florentina Belciug Martina Carducci Virginia Cianchi Casey Zakroff Salvatore Durante Caroline Zellmer Stephen Baker Thomas D. Stanton Kathryn E. Holt Kelly Wyres Neil Ravenscroft Gianmarco Gasperini Omar Rossi Carlo Giannelli Francesco Berlanda Scorza Francesca Micoli The characterization of Klebsiella pneumoniae associated with neonatal sepsis in low- and middle-income countries to inform vaccine design Communications Biology |
| title | The characterization of Klebsiella pneumoniae associated with neonatal sepsis in low- and middle-income countries to inform vaccine design |
| title_full | The characterization of Klebsiella pneumoniae associated with neonatal sepsis in low- and middle-income countries to inform vaccine design |
| title_fullStr | The characterization of Klebsiella pneumoniae associated with neonatal sepsis in low- and middle-income countries to inform vaccine design |
| title_full_unstemmed | The characterization of Klebsiella pneumoniae associated with neonatal sepsis in low- and middle-income countries to inform vaccine design |
| title_short | The characterization of Klebsiella pneumoniae associated with neonatal sepsis in low- and middle-income countries to inform vaccine design |
| title_sort | characterization of klebsiella pneumoniae associated with neonatal sepsis in low and middle income countries to inform vaccine design |
| url | https://doi.org/10.1038/s42003-025-08258-7 |
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