Lethal CD4 T Cell Responses Induced by Vaccination Against Staphylococcus aureus Bacteremia
Lethal CD4 T Cell Responses Induced by Vaccination Against Staphylococcus aureus Bacteremia
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DOI：
10.1093/infdis/jix096
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发表时间：
2017-04-15
影响因子：
6.4
通讯作者：
Datta, Sandip K.
中科院分区：
文献类型：
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作者：
Karauzum, Hatice;Haudenschild, Christian C.;Datta, Sandip K.
针对金黄色葡萄球菌感染的多种候选疫苗在临床试验中失败。对最近一项过早停止的疫苗试验的分析显示，手术后感染S。金黄色葡萄球菌感染的发展，强调潜在的诱导有害的免疫反应，需要更好地了解保护性免疫的要求，对金黄色葡萄球菌。金黄色。单抗原疫苗的这些失败促使了针对众多S.金黄色葡萄球菌毒力因子在目前的研究中，我们使用致死性辐照的S。金黄色葡萄球菌作为模型多组分疫苗，并显示小鼠的疫苗接种降低了菌血症攻击模型中的存活率。这些有害作用是由于CD4 T细胞依赖性干扰素。免疫应答，并且可以通过在疫苗接种期间抑制这种应答的发展来预防。我们的研究结果确定了疫苗接种诱导病理性免疫反应的可能性，并对最近的疫苗失败和未来葡萄球菌疫苗的设计产生了影响。
Multiple candidate vaccines against Staphylococcus aureus infections have failed in clinical trials. Analysis of a recent prematurely halted vaccine trial revealed increased mortality rates among vaccine recipients in whom postsurgical S. aureus infection developed, emphasizing the potential for induction of detrimental immune responses and the need to better understand the requirements for protective immunity against S. aureus. These failures of single-antigen vaccines have prompted ongoing development of multicomponent vaccines to target the multitude of S. aureus virulence factors. In the current study, we used lethally irradiated S. aureus as a model multicomponent vaccine and showed that vaccination of mice decreased survival in a bacteremia challenge model. These deleterious effects were due to a CD4 T-cell-dependent interferon. response and could be prevented by inhibiting development of this response during vaccination. Our results identify the potential for vaccination to induce pathological immune responses, and they have implications for recent vaccine failures and the design of future staphylococcal vaccines.