Flagella hook protein FlgE is a novel vaccine candidate of Pseudomonas aeruginosa identified by a genomic approach. Issue 17 (22nd April 2021)

• Record Type: Journal Article
• Authors: Wan, Chuang; Gao, Chen; Xie, Qin; Wang, Yin; Cheng, Xin; Fang, Yao; Liu, Zhiyong; Zhang, Weijun; Zou, Quanming; Lu, Guangwen; Gu, Jiang
• Is Part Of: Vaccine. Volume 39:Issue 17(2021)
• Page Start: 2386
• Page End: 2395
• Publication Date: 2021-04-22
• Subjects: Genomic library -- Antigen screening -- Pseudomonas aeruginosa -- FlgE -- Pneumonia; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.03.051
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: A genome-wide library of Pseudomonas aeruginosa protein fragments was constructed. The flagella hook protein FlgE is a novel vaccine candidate for Pseudomonas aeruginosa . The combination of recombinant FlgE with PcrVNH elevates the protection against Pseudomonas aeruginosa. Abstract: Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens.