Invasive Staphylococcus aureus infections are a leading cause of morbidity and mortality in both hospital and community settings, especially with the widespread emergence of virulent and multi-drug resistant methicillin-resistant S. aureus strains. There is an urgent and unmet clinical need for non-antibiotic immune-based approaches to treat these infections as the increasing antibiotic resistance is creating a serious threat to public health. However, all vaccination attempts aimed at preventing S. aureus invasive infections have failed in human trials, especially all vaccines aimed at generating high titers of opsonic antibodies against S. aureus surface antigens to facilitate antibody-mediated bacterial clearance. In this review, we summarize the data from humans regarding the immune responses that protect against invasive S. aureus infections as well as host genetic factors and bacterial evasion mechanisms, which are important to consider for the future development of effective and successful vaccines and immunotherapies against invasive S. aureus infections in humans. The evidence presented form the basis for a hypothesis that staphylococcal toxins (including superantigens and pore-forming toxins) are important virulence factors, and targeting the neutralization of these toxins are more likely to provide a therapeutic benefit in contrast to prior vaccine attempts to generate antibodies to facilitate opsonophagocytosis.

中文翻译：

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抗金黄色葡萄球菌侵袭性感染疫苗的开发：基于人类免疫力，遗传学和细菌逃逸机制的证据。

在医院和社区环境中，侵入性金黄色葡萄球菌感染是发病率和死亡率的主要原因，尤其是随着强毒和多药耐甲氧西林金黄色葡萄球菌菌株的广泛出现。临床上迫切需要解决基于非抗生素免疫的方法来治疗这些感染的问题，因为不断增加的抗生素耐药性正在严重威胁公共卫生。但是，所有旨在预防金黄色葡萄球菌侵入性感染的疫苗接种尝试在人体试验中均告失败，尤其是所有旨在产生高滴度针对金黄色葡萄球菌表面抗原的调理抗体以促进抗体介导的细菌清除的疫苗。在这篇综述中，我们总结了来自人类的有关防御侵袭性S的免疫反应的数据。金黄色葡萄球菌感染以及宿主遗传因素和细菌逃逸机制，对于将来针对人类侵袭性金黄色葡萄球菌感染的有效和成功的疫苗和免疫疗法的发展，考虑重要的因素。所提供的证据构成了以下假设的基础：葡萄球菌毒素（包括超抗原和成孔毒素）是重要的毒力因子，与以前疫苗尝试产生抗体的尝试相反，针对这些毒素的中和作用更有可能提供治疗益处促进调理吞噬作用。