A Staphylococcus aureus four-antigen vaccine (SA4Ag) was designed for the prevention of invasive disease in surgical patients. The vaccine is composed of capsular polysaccharide type 5 and type 8 CRM₁₉₇ conjugates, a clumping factor A mutant (Y338A-ClfA) and manganese transporter subunit C (MntC). S. aureus pathogenicity is characterized by an ability to rapidly adapt to the host environment during infection, which can progress from a local infection to sepsis and invasion of distant organs. To test the protective capacity of the SA4Ag vaccine against progressive disease stages of an invasive S. aureus infection, a deep tissue infection mouse model, a bacteremia mouse model, a pyelonephritis model, and a rat model of infectious endocarditis were utilized. SA4Ag vaccination significantly reduced the bacterial burden in deep tissue infection, in bacteremia, and in the pyelonephritis model. Complete prevention of infection was demonstrated in a clinically relevant endocarditis model. Unfortunately, these positive preclinical findings with SA4Ag did not prove the clinical utility of SA4Ag in the prevention of surgery-associated invasive S. aureus infection.

中文翻译：

---

四抗原金黄色葡萄球菌疫苗在侵袭性金黄色葡萄球菌疾病的临床前模型中的表现

一个金黄色葡萄球菌四抗原疫苗（SA4Ag）是专为手术患者预防侵袭性疾病。该疫苗由5型和8型CRM ₁₉₇荚膜多糖缀合物，聚集因子A突变体（Y338A-ClfA）和锰转运蛋白亚基C（MntC）组成。金黄色葡萄球菌的致病性的特征在于在感染期间能够迅速适应宿主环境的能力，该能力可以从局部感染发展为败血症和远处器官的侵袭。测试SA4Ag疫苗对侵袭性金黄色葡萄球菌进行性疾病阶段的保护能力感染，深部组织感染小鼠模型，菌血症小鼠模型，肾盂肾炎模型和感染性心内膜炎的大鼠模型被利用。SA4Ag疫苗接种可大大减少深部组织感染，菌血症和肾盂肾炎模型中的细菌负担。在临床相关的心内膜炎模型中证明了感染的完全预防。不幸的是，这些SA4Ag的临床前阳性结果并未证明SA4Ag在预防与手术有关的侵袭性金黄色葡萄球菌感染中的临床效用。