Genome-Based Approach Delivers Vaccine Candidates Against Pseudomonas aeruginosa
Genome-Based Approach Delivers Vaccine Candidates Against Pseudomonas aeruginosa
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DOI：
10.3389/fimmu.2018.03021
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发表时间：
2019-01-09
影响因子：
7.3
通讯作者：
Bragonzi, Alessandra
中科院分区：
文献类型：
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作者：
Bianconi, Irene;Alcala-Franco, Beatriz;Bragonzi, Alessandra
铜绿假单胞菌感染的高发病率、严重性和不断增加的抗生素耐药性，凸显了对新治疗方案的需求。预防或限制铜绿假单胞菌感染的疫苗接种策略是积极影响高危患者临床结果的合理方法；尽管如此，这种细菌仍然是一个具有挑战性的疫苗目标。为了确定新型候选疫苗，我们从铜绿假单胞菌参考菌株 PAO1 的基因组序列分析开始，探索与其他生物信息学工具相结合的反向疫苗学方法。生物信息学方法选出了 52 种潜在抗原。这些候选疫苗在不同来源的铜绿假单胞菌基因组中以及从囊性纤维化患者纵向分离的菌株中是保守的。为了评估单一抗原或抗原组合对铜绿假单胞菌感染的免疫保护作用，在急性呼吸道感染的小鼠模型中建立了疫苗接种方案。选定的候选物的组合，而不是单一抗原，可以有效控制小鼠肺炎体内模型中的铜绿假单胞菌感染。五种组合能够显着提高受攻击小鼠的存活率，并且全部都包含 PA5340，这是一种仅存在于铜绿假单胞菌中的假设蛋白质。 PA5340 与 PA3526-MotY 结合提供了最大程度的保护。两种蛋白质通过免疫荧光暴露在表面并引发特异性免疫反应。这两种蛋白质抗原的组合可能代表一种预防铜绿假单胞菌感染的潜在疫苗。
High incidence, severity and increasing antibiotic resistance characterize Pseudomonas aeruginosa infections, highlighting the need for new therapeutic options. Vaccination strategies to prevent or limit P. aeruginosa infections represent a rational approach to positively impact the clinical outcome of risk patients; nevertheless this bacterium remains a challenging vaccine target. To identify novel vaccine candidates, we started from the genome sequence analysis of the P. aeruginosa reference strain PAO1 exploring the reverse vaccinology approach integrated with additional bioinformatic tools. The bioinformatic approaches resulted in the selection of 52 potential antigens. These vaccine candidates were conserved in P. aeruginosa genomes from different origin and among strains isolated longitudinally from cystic fibrosis patients. To assess the immune-protection of single or antigens combination against P. aeruginosa infection, a vaccination protocol was established in murine model of acute respiratory infection. Combinations of selected candidates, rather than single antigens, effectively controlled P. aeruginosa infection in the in vivo model of murine pneumonia. Five combinations were capable of significantly increase survival rate among challenged mice and all included PA5340, a hypothetical protein exclusively present in P. aeruginosa. PA5340 combined with PA3526-MotY gave the maximum protection. Both proteins were surface exposed by immunofluorescence and triggered a specific immune response. Combination of these two protein antigens could represent a potential vaccine to prevent P. aeruginosa infection.