Nonne Francesca, Molfetta Mariagrazia, Belciug Gianina Florentina, Carducci Martina, Cianchi Virginia, Zakroff Casey, Durante Salvatore, Zellmer Caroline, Baker Stephen, Stanton Thomas D, Holt Kathryn E, Wyres Kelly, Ravenscroft Neil, Gasperini Gianmarco, Rossi Omar, Giannelli Carlo, Berlanda Scorza Francesco, Micoli Francesca
GSK Vaccines Institute for Global Health (GVGH), Siena, Italy.
Department of Biomedical Sciences, Humanitas University, Milan, Italy.
Commun Biol. 2025 Jun 9;8(1):898. doi: 10.1038/s42003-025-08258-7.
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.
肺炎克雷伯菌是新生儿败血症的主要病因，与抗菌药物耐药性密切相关，目前尚无可用疫苗。K抗原（KAg）已被确定为潜在靶点，但其多样性使疫苗开发具有挑战性。另外，使用包膜下O抗原（OAg）也引发了关于抗体可及性的问题。我们对BARNARDS研究中的临床分离株进行了特征分析，该研究旨在确定低收入和中等收入国家新生儿败血症的负担。通过多糖的结构分析验证了基因组预测。针对常见KAg和OAg产生的抗体能结合所有同源生物体，而不考虑特定的多糖结构特征。有趣的是，抗KAg抗体对相当数量分离株的杀菌活性与抗OAg抗体相当。多糖特征与肺炎克雷伯菌的杀菌易感性之间没有关联。观察到不同KAg之间的抗体交叉反应，以及OAg抗体之间广泛的交叉反应。本研究有助于确定预防肺炎克雷伯菌引起的新生儿败血症的最佳疫苗组成。
