Kramarska Eliza, Toumi Eya, Squeglia Flavia, Laverde Diana, Napolitano Valeria, Frapy Eric, Autiero Ida, Sadones Oceane, Huebner Johannes, Skurnik David, Romero-Saavedra Felipe, Berisio Rita
Institute of Biostructures and Bioimaging, Italian Research Council (CNR), Naples, Italy.
CNRS, INSERM, Institut Necker-Enfants Malades, U1151-Equipe 11, Faculté de Médecine, University of Paris City, Paris, France.
NPJ Vaccines. 2024 Aug 18;9(1):151. doi: 10.1038/s41541-024-00940-x.
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). We demonstrate that antibodies raised against Sc(EH) 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) is a promising antigen for the development of vaccines against different Gram-positive pathogens.
ESKAPE病原体在全球范围内导致复杂的医院感染，并且在临床环境中常常对常用抗生素耐药。在ESKAPE病原体中，耐万古霉素屎肠球菌（VREfm）和耐甲氧西林金黄色葡萄球菌（MRSA）是两种重要的革兰氏阳性病原体，迫切需要非抗生素替代物。我们之前表明，屎肠球菌的脂蛋白AdcA能引发针对屎肠球菌和粪肠球菌的调理和保护性抗体。基于我们在此报告的观察结果，即AdcA还能引发针对MRSA和其他临床相关革兰氏阳性病原体的调理抗体，我们鉴定出了负责AdcA交叉反应活性的主要表位，并设计了一种超耐热且多表位呈现的抗原Sc(EH)。我们证明，针对Sc(EH)产生的抗体介导了对包括VREfm和MRSA在内的多种革兰氏阳性病原体的调理杀伤作用，并在被动和主动免疫模型中都提供了保护。我们的数据表明，Sc(EH)是开发针对不同革兰氏阳性病原体疫苗的一种有前景的抗原。
