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Recent developments for Staphylococcus aureus vaccines: clinical and basic science challenges

机译：金黄色葡萄球菌疫苗的最新发展：临床和基础科学挑战

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Bacterial vaccines have made dramatic impacts upon morbidity and mortality caused by a number of common pathogens, but a vaccine to prevent Staphylococcus aureus infections has proven to be illusive. With successful bacterial vaccines, the organisms are all part of the transient flora, whereas, S. aureus is part of the normal human flora. This means that S. aureus has had a prolonged time to adapt to the host milieu and its defences. The failure of several staphylococcal antigens to protect humans from infection in vaccine clinical trials using active or passive immunisation has stimulated a re-examination of the fundamental assumptions about staphylococcal immunity in humans vs. animals, especially rodents. This has spurred an active debate about the appropriate models for vaccine development and an examination of our current understanding of the protective immunity in humans. A major factor in the development of previous bacterial vaccines was a biomarker that predicted human protection, e.g., antibodies to tetanus toxoid or to pneumococcal polysaccharide. While antibodies against a number of staphylococcal antigens have proven to be an excellent biomarker for protection in rodents, these have not been translated to human infections. Thus, while much work remains, there is a growing consensus that T-cell immunity plays an important role in protecting humans. Moreover, the presence of anti-staphylococcal toxin antibodies correlates with reduced disease severity in humans. The most important recent advances concerning potential biomarkers, and the role of pre-existing immune status of vaccines in vaccine-associated mortality are considered in this review.
机译：细菌疫苗对由多种常见病原体引起的发病率和死亡率产生了巨大影响，但是预防金黄色葡萄球菌感染的疫苗已被证明是虚幻的。使用成功的细菌疫苗，这些生物都是瞬时菌群的一部分，而金黄色葡萄球菌是正常人类菌群的一部分。这意味着金黄色葡萄球菌已经有较长的时间适应宿主环境及其防御。在使用主动或被动免疫的疫苗临床试验中，几种葡萄球菌抗原未能保护人类免受感染，这刺激了人们对动物，尤其是啮齿动物对葡萄球菌免疫的基本假设的重新审查。这激起了关于疫苗开发适当模型的积极辩论，并检验了我们目前对人类保护性免疫的理解。以前细菌疫苗开发的主要因素是预测人类保护作用的生物标志物，例如抗破伤风类毒素或肺炎球菌多糖的抗体。虽然针对多种葡萄球菌抗原的抗体已被证明是在啮齿动物中提供保护的极佳生物标志物，但尚未将其转化为人类感染。因此，尽管还有很多工作要做，但越来越多的共识是T细胞免疫在保护人类方面起着重要作用。此外，抗葡萄球菌毒素抗体的存在与人类疾病严重程度降低有关。在这篇综述中考虑了有关潜在生物标志物的最新最重要进展，以及预先存在的免疫状态在疫苗相关死亡率中的作用。

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