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An X-ray inactivated vaccine against Pseudomonas aeruginosa Keratitis in mice
Boguang Jiang1, Yingjie Luo1, Naihong Yan2
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China.
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.
Insights
A novel X-ray inactivated vaccine (XPa) shows promise in preventing Pseudomonas aeruginosa keratitis, a leading cause of blindness. Vaccination reduces bacterial load and inflammation, preserving vision in a mouse model.
Area of Science:
- Ophthalmology
- Microbiology
- Immunology
Background:
- Bacterial keratitis, a significant cause of global blindness, is frequently caused by Pseudomonas aeruginosa.
- Increasing multidrug resistance in P. aeruginosa limits effective antibiotic treatments.
- There is a critical need for alternative therapeutic strategies, such as vaccines, to combat P. aeruginosa infections.
Purpose of the Study:
- To evaluate the protective efficacy of an X-ray inactivated vaccine (XPa) against P. aeruginosa keratitis.
- To investigate the underlying immunological mechanisms of XPa-induced protection.
- To assess the potential of XPa as a vaccine candidate for bacterial keratitis.
Main Methods:
- A murine model of P. aeruginosa keratitis was established.
- Mice were immunized with the XPa vaccine.
- Corneal bacterial load, pathology scores, macrophage polarization, fibroblast activation, and visual impairment were assessed.
Main Results:
- XPa vaccination significantly reduced corneal bacterial loads and associated pathology scores.
- Vaccination promoted M2 macrophage polarization in the cornea, mitigating excessive inflammation.
- Histological analysis revealed suppressed corneal fibroblast activation and prevention of irreversible visual impairment.
Conclusions:
- The XPa vaccine demonstrates significant protective effects against P. aeruginosa keratitis in a murine model.
- XPa vaccination modulates the immune response by promoting M2 macrophage polarization and suppressing detrimental fibroblast activation.
- XPa represents a promising vaccine candidate for preventing and treating P. aeruginosa-induced bacterial keratitis.
