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小鼠铜绿假单胞菌角膜炎的 X 射线灭活疫苗。

An X-ray inactivated vaccine against Pseudomonas aeruginosa Keratitis in mice.

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.

Research Laboratory of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Vaccine. 2023 Jul 19;41(32):4700-4709. doi: 10.1016/j.vaccine.2023.05.066. Epub 2023 Jun 21.

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is one of the most prevalent pathogens of bacterial keratitis. Bacterial keratitis is a major cause of blindness worldwide. The rising incidence of multidrug resistance of P. aeruginosa precludes treatment with conventional antibiotics. Herein, we evaluated the protective efficiency and explored the possible underlying mechanism of an X-ray inactivated vaccine (XPa) using a murine P. aeruginosa keratitis model. Mice immunized with XPa exhibit reduced corneal bacterial loads and pathology scores. XPa vaccination induced corneal macrophage polarization toward M2, averting an excessive inflammatory reaction. Furthermore, histological observations indicated that XPa vaccination suppressed corneal fibroblast activation and prevented irreversible visual impairment. The potency of XPa against keratitis highlights its potential utility as an effective and promising vaccine candidate for P. aeruginosa.

摘要

铜绿假单胞菌(P. aeruginosa)是细菌性角膜炎最常见的病原体之一。细菌性角膜炎是全球致盲的主要原因。铜绿假单胞菌对抗生素的多重耐药性不断上升,使得传统抗生素的治疗方法变得不可行。在此,我们使用小鼠铜绿假单胞菌角膜炎模型评估了 X 射线灭活疫苗(XPa)的保护效率,并探讨了其可能的潜在机制。用 XPa 免疫的小鼠角膜细菌载量和病理评分降低。XPa 疫苗接种诱导角膜巨噬细胞向 M2 极化,避免了过度的炎症反应。此外,组织学观察表明,XPa 疫苗接种抑制了角膜成纤维细胞的激活,防止了不可逆转的视力损害。XPa 对角膜炎的疗效突出了其作为一种有效和有前途的铜绿假单胞菌候选疫苗的潜在用途。

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