a Department of Medical Microbiology , University of Groningen, University Medical Center Groningen , Hanzeplein 1, Groningen , RB , The Netherlands.
b Department of Orthopaedic Surgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Virulence. 2018 Jan 1;9(1):262-272. doi: 10.1080/21505594.2017.1403004. Epub 2017 Dec 26.
Staphylococcus aureus infections are a major threat in healthcare, requiring adequate early-stage diagnosis and treatment. This calls for novel diagnostic tools that allow noninvasive in vivo detection of staphylococci. Here we performed a preclinical study to investigate a novel fully-human monoclonal antibody 1D9 that specifically targets the immunodominant staphylococcal antigen A (IsaA). We show that 1D9 binds invariantly to S. aureus cells and may further target other staphylococcal species. Importantly, using a human post-mortem implant model and an in vivo murine skin infection model, preclinical feasibility was demonstrated for 1D9 labeled with the near-infrared fluorophore IRDye800CW to be applied for direct optical imaging of in vivo S. aureus infections. Additionally, Zirconium-labeled 1D9 could be used for positron emission tomography imaging of an in vivo S. aureus thigh infection model. Our findings pave the way towards clinical implementation of targeted imaging of staphylococcal infections using the human monoclonal antibody 1D9.
金黄色葡萄球菌感染是医疗保健领域的一个主要威胁，需要进行充分的早期诊断和治疗。这就需要新的诊断工具，能够实现对葡萄球菌的非侵入性体内检测。在这里，我们进行了一项临床前研究，以调查一种新型的、完全人源化的单克隆抗体 1D9，该抗体特异性靶向免疫显性葡萄球菌抗原 A（IsaA）。我们表明，1D9 不变地结合到金黄色葡萄球菌细胞上，并且可能进一步靶向其他葡萄球菌物种。重要的是，使用人体死后植入物模型和体内小鼠皮肤感染模型，证明了用近红外荧光染料 IRDye800CW 标记的 1D9 用于体内金黄色葡萄球菌感染的直接光学成像的临床前可行性。此外，用锆标记的 1D9 可用于体内金黄色葡萄球菌大腿感染模型的正电子发射断层扫描成像。我们的研究结果为使用人源单克隆抗体 1D9 对葡萄球菌感染进行靶向成像的临床实施铺平了道路。
