Evaluation of Genetically Inactivated Alpha Toxin for Protection in Multiple Mouse Models of Staphylococcus aureus Infection
Evaluation of Genetically Inactivated Alpha Toxin for Protection in Multiple Mouse Models of Staphylococcus aureus Infection
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DOI：
10.1371/journal.pone.0063040
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发表时间：
2013-04-29
期刊：
影响因子：
3.7
通讯作者：
Burns, Drusilla L.
中科院分区：
文献类型：
--
作者：
Brady, Rebecca A.;Mocca, Christopher P.;Burns, Drusilla L.
金黄色葡萄球菌是一种主要的人类病原体，也是医院和社区获得性感染的主要原因。开发针对该病原体的疫苗是一个重要目标。而S.金黄色葡萄球菌保护性抗原已经在文献中鉴定，但大多数仅在单一动物疾病模型中进行了测试。我们希望评估一个S的能力。金黄色葡萄球菌疫苗抗原在多种小鼠模型中进行保护，从而评估一种模型中的保护是否转化为其他模型中的保护，包括病原体可能引起的全部感染。我们选择专注于遗传失活的α毒素突变体HlaH35L。我们在三种感染模型中使用相同的疫苗剂量、方案、免疫途径、佐剂和攻毒株评价了该抗原提供的保护。当用HlaH35L免疫小鼠并通过皮肤和软组织感染模型攻击时，HlaH35L免疫导致较轻的感染和减少S.与对照相比，激发部位的金黄色葡萄球菌水平。使用全身感染模型攻击HlaH35L免疫的小鼠，与对照小鼠相比，细菌定殖的减少有限，但具有统计学意义。相反，在慢性生物膜感染的假体植入物模型中，与对照相比，细菌水平没有显著差异。这些结果表明，疫苗可以提供针对一种形式的S的保护。金黄色葡萄球菌疾病而不赋予对其他疾病表现的保护，因此强调了在金黄色葡萄球菌中的重大挑战。金黄色葡萄球菌疫苗开发。
Staphylococcus aureus is a major human pathogen and a leading cause of nosocomial and community-acquired infections. Development of a vaccine against this pathogen is an important goal. While S. aureus protective antigens have been identified in the literature, the majority have only been tested in a single animal model of disease. We wished to evaluate the ability of one S. aureus vaccine antigen to protect in multiple mouse models, thus assessing whether protection in one model translates to protection in other models encompassing the full breadth of infections the pathogen can cause. We chose to focus on genetically inactivated alpha toxin mutant HlaH35L. We evaluated the protection afforded by this antigen in three models of infection using the same vaccine dose, regimen, route of immunization, adjuvant, and challenge strain. When mice were immunized with HlaH35L and challenged via a skin and soft tissue infection model, HlaH35L immunization led to a less severe infection and decreased S. aureus levels at the challenge site when compared to controls. Challenge of HlaH35L-immunized mice using a systemic infection model resulted in a limited, but statistically significant decrease in bacterial colonization as compared to that observed with control mice. In contrast, in a prosthetic implant model of chronic biofilm infection, there was no significant difference in bacterial levels when compared to controls. These results demonstrate that vaccines may confer protection against one form of S. aureus disease without conferring protection against other disease presentations and thus underscore a significant challenge in S. aureus vaccine development.