Klimka Alexander, Mertins Sonja, Nicolai Anne Kristin, Rummler Liza Marie, Higgins Paul G, Günther Saskia Diana, Tosetti Bettina, Krut Oleg, Krönke Martin
Institute for Medical Microbiology, Immunology and Hygiene, University Hospital Cologne, Cologne, Germany.
German Center for Infection Research (DZIF), Partner site Bonn-Cologne, Cologne, Germany.
NPJ Vaccines. 2021 Jan 18;6(1):11. doi: 10.1038/s41541-020-00268-2.
Staphylococcus aureus represents a serious infectious threat to global public health and a vaccine against S. aureus represents an unmet medical need. We here characterise two S. aureus vaccine candidates, coproporphyrinogen III oxidase (CgoX) and triose phosphate isomerase (TPI), which fulfil essential housekeeping functions in heme synthesis and glycolysis, respectively. Immunisation with rCgoX and rTPI elicited protective immunity against S. aureus bacteremia. Two monoclonal antibodies (mAb), CgoX-D3 and TPI-H8, raised against CgoX and TPI, efficiently provided protection against S. aureus infection. MAb-CgoX-D3 recognised a linear epitope spanning 12 amino acids (aa), whereas TPI-H8 recognised a larger discontinuous epitope. The CgoX-D3 epitope conjugated to BSA elicited a strong, protective immune response against S. aureus infection. The CgoX-D3 epitope is highly conserved in clinical S. aureus isolates, indicating its potential wide usability against S. aureus infection. These data suggest that immunofocusing through epitope-based immunisation constitutes a strategy for the development of a S. aureus vaccine with greater efficacy and better safety profile.
金黄色葡萄球菌对全球公共卫生构成严重的感染威胁，而针对金黄色葡萄球菌的疫苗仍是未满足的医学需求。我们在此对两种金黄色葡萄球菌疫苗候选物进行了表征，即粪卟啉原III氧化酶（CgoX）和磷酸丙糖异构酶（TPI），它们分别在血红素合成和糖酵解中发挥基本的管家功能。用重组CgoX和重组TPI免疫可引发针对金黄色葡萄球菌菌血症的保护性免疫。针对CgoX和TPI产生的两种单克隆抗体（mAb），即CgoX-D3和TPI-H8，能有效提供针对金黄色葡萄球菌感染的保护。单克隆抗体CgoX-D3识别一个跨越12个氨基酸（aa）的线性表位，而TPI-H8识别一个更大的不连续表位。与牛血清白蛋白（BSA）偶联的CgoX-D3表位引发了针对金黄色葡萄球菌感染的强烈保护性免疫反应。CgoX-D3表位在临床金黄色葡萄球菌分离株中高度保守，表明其对金黄色葡萄球菌感染具有潜在的广泛适用性。这些数据表明，基于表位的免疫聚焦构成了一种开发具有更高疗效和更好安全性的金黄色葡萄球菌疫苗的策略。
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