Division of HIV, Infectious Diseases and Global Medicine, Department of Medicine, University of California, San Francisco.
Integrated Biotherapeutics, Inc, Rockville, Maryland.
J Infect Dis. 2020 Jan 2;221(2):267-275. doi: 10.1093/infdis/jiz437.
Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, with pneumonia being one of the most severe infections. In as much as staphylococcal pneumonia is a disease driven in large part by α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization with attenuated forms of Hla (HlaH35L/H48L) alone, PVL components (LukS-PVT28F/K97A/S209A and LukF-PVK102A) alone, or combination of all 3 toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S. aureus (MRSA). Rabbits vaccinated with Hla toxoid alone or PVL components alone were only partially protected against lethal pneumonia, whereas those vaccinated with all 3 toxoids had 100% protection against lethality. Vaccine-mediated protection correlated with induction of polyclonal antibody response that neutralized not only α-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.
金黄色葡萄球菌是一种常见的病原体，可引起人类不同严重程度的感染，其中肺炎是最严重的感染之一。鉴于金黄色葡萄球菌肺炎在很大程度上是由α-溶血素（Hla）和金葡菌杀白细胞素（PVL）驱动的疾病，我们评估了单独使用减毒形式的 Hla（HlaH35L/H48L）、PVL 成分（LukS-PVT28F/K97A/S209A 和 LukF-PVK102A）或所有 3 种类毒素的组合是否可以预防由美国 300 型社区获得性耐甲氧西林金黄色葡萄球菌（MRSA）引起的坏死性肺炎的兔模型中的致死性挑战。单独接种 Hla 类毒素或 PVL 成分的兔子仅部分免受致死性肺炎的保护，而接种所有 3 种类毒素的兔子则 100%免受致死性的影响。疫苗介导的保护与多克隆抗体反应的诱导相关，该反应不仅中和了 α-溶血素和 PVL，还中和了美国 300 型和其他流行的 MRSA 克隆产生的其他相关毒素。
