A Serologic Correlate of Protective Immunity Against Community-Onset Staphylococcus aureus Infection
A Serologic Correlate of Protective Immunity Against Community-Onset Staphylococcus aureus Infection
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DOI：
10.1093/cid/cit123
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发表时间：
2013-06-01
影响因子：
11.8
通讯作者：
Hunstad, David A.
中科院分区：
文献类型：
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作者：
Fritz, Stephanie A.;Tiemann, Kristin M.;Hunstad, David A.
背景金黄色葡萄球菌是人类感染的主要原因之一。广泛的耐药性、强毒株的出现以及S.金黄色葡萄球菌定殖>30%的人类群体有助于该生物体的致病成功。人对S.金黄色葡萄球菌及其与保护性免疫的关系仍不完全确定，挑战有效疫苗的战略发展。我们测量了对2种葡萄球菌外毒素，α-溶血素（Hla）和Panton-Valentine杀白细胞素（PVL; LukF-PV/LukS-PV亚基）的体液应答，这两种外毒素都是当前疫苗和免疫疗法开发的首要靶点。我们对235名儿童链球菌感染者的急性期和恢复期血清抗体水平与12个月随访期间复发感染的发生率进行了相关性研究。金黄色葡萄球菌定植、原发性或复发性皮肤和软组织感染或侵袭性疾病。皮肤感染引起抗Hla和抗PVL抗体的短暂增加;然而，随后的感染风险在原发性和复发性皮肤感染队列之间是相似的。侵袭性感染的患者对Hla和LukF的预先存在的滴度最低，但显示出最高的恢复期滴度。在不同的队列中，恢复期抗Hla滴度与对随后的S。金黄色葡萄球菌感染。皮肤S.金黄色葡萄球菌感染不能可靠地引起持久的保护性免疫应答。这项研究提供了第一个联系之间的保护，从疾病复发和体液反应Hla，一个毒力因子已经牵连在疾病的发病机制。这些观察结果可用于改进正在进行的疫苗和免疫治疗工作，并为临床试验的设计提供信息。
Background. Staphylococcus aureus is among the leading causes of human infection. Widespread drug resistance, emergence of highly virulent strains, and the ability of S. aureus to colonize >30% of the human population contribute to this organism's pathogenic success. Human serologic responses to S. aureus and their relationship to protective immunity remain incompletely defined, challenging the strategic development of efficacious vaccines.Methods. We measured humoral responses to 2 staphylococcal exotoxins, alpha-hemolysin (Hla) and Panton-Valentine leukocidin (PVL; LukF-PV/LukS-PV subunits), both premier targets of current vaccine and immunotherapy development. We correlated acute and convalescent serum antibody levels with incidence of recurrent infection over 12 months follow-up in 235 children with S. aureus colonization, primary or recurrent skin and soft tissue infection, or invasive disease.Results. Cutaneous infection elicited transient increases in anti-Hla and anti-PVL antibodies; however, subsequent infection risk was similar between primary and recurrent cutaneous infection cohorts. Patients with invasive infections had the lowest preexisting titers against Hla and LukF but displayed the highest convalescent titers. Across cohorts, convalescent anti-Hla titers correlated with protection against subsequent S. aureus infection.Conclusions. Cutaneous S. aureus infection does not reliably provoke durable, protective immune responses. This study provides the first link between protection from disease recurrence and the humoral response to Hla, a virulence factor already implicated in disease pathogenesis. These observations can be utilized to refine ongoing vaccine and immunotherapy efforts and inform the design of clinical trials.