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脱毒白细胞毒素 AB 疫苗接种可降低金黄色葡萄球菌小型猪深部外科感染模型中的细菌负荷。

Vaccination With Detoxified Leukocidin AB Reduces Bacterial Load in a Staphylococcus aureus Minipig Deep Surgical Wound Infection Model.

机构信息

Bacterial Vaccines, Spring House, Pennsylvania,USA.

Janssen Vaccines and Prevention B.V., Leiden,The Netherlands.

出版信息

J Infect Dis. 2022 Apr 19;225(8):1460-1470. doi: 10.1093/infdis/jiab219.

Abstract

Vaccines against Staphylococcus aureus have eluded researchers for >3 decades while the burden of staphylococcal diseases has increased. Early vaccine attempts mainly used rodents to characterize preclinical efficacy, and all subsequently failed in human clinical efficacy trials. More recently, leukocidin AB (LukAB) has gained interest as a vaccine antigen. We developed a minipig deep surgical wound infection model offering 3 independent efficacy readouts: bacterial load at the superficial and at the deep-seated surgical site, and dissemination of bacteria. Due to similarities with humans, minipigs are an attractive option to study novel vaccine candidates. With this model, we characterized the efficacy of a LukAB toxoid as vaccine candidate. Compared to control animals, a 3-log reduction of bacteria at the deep-seated surgical site was observed in LukAB-treated minipigs and dissemination of bacteria was dramatically reduced. Therefore, LukAB toxoids may be a useful addition to S. aureus vaccines and warrant further study.

摘要

金黄色葡萄球菌疫苗的研究已经超过 30 年,但葡萄球菌病的负担却在增加。早期的疫苗尝试主要使用啮齿动物来描述临床前疗效,而所有这些疫苗随后在人体临床疗效试验中均失败。最近,白细胞毒素 AB(LukAB)作为疫苗抗原引起了人们的兴趣。我们开发了一种小型猪深部手术感染模型,提供了 3 个独立的疗效评价指标:浅层和深部手术部位的细菌载量,以及细菌的传播。由于与人类的相似性,小型猪是研究新型疫苗候选物的一个有吸引力的选择。使用该模型,我们研究了 LukAB 类毒素作为疫苗候选物的疗效。与对照组动物相比,LukAB 处理的小型猪深部手术部位的细菌数量减少了 3 个对数级,细菌的传播也显著减少。因此,LukAB 类毒素可能是金黄色葡萄球菌疫苗的有益补充,并值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8d4/9016470/632a16ba4bb0/jiab219f0001.jpg

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