The O-glycan is essential for the induction of protective antibodies against lethal infection by flagella A-bearing Pseudomonas aeruginosa

• DOI: 10.1128/iai.00427-23
• Publication Date: 2024-02-23T14:00:59Z
• Authors: Myeongjin Choi; Surekha Shridhar; Heather Fox; Kun Luo; Mohammed N. Amin; Sharon M. Tennant; Raphael Simon; Alan S. Cross
• Keywords: Flagellin

ABSTRACT To address the problem of increased antimicrobial resistance, we developed a glycoconjugate vaccine comprised O-polysaccharides (OPS) four most prevalent serotypes Klebsiella pneumoniae (KP) linked to recombinant flagellin types A and B (rFlaA rFlaB) Pseudomonas aeruginosa (PA). Flagellin is major subunit flagellar filament. Flagella B, essential virulence factors for PA, are glycosylated with different glycans. We previously reported that while both rFlaA rFlaB were highly immunogenic, only antisera reduced PA motility protected mice from lethal infection in mouse model thermal injury. Since not glycosylated, examined possibility glycan on native FlaA (nFlaA) might be critical functional immune responses. compared ability nFlaA native, deglycosylated (dnFlaA) induce functionally active antisera. O was removed trifluoromethanesulfonic acid. Despite similar high-titered anti-FlaA antibody levels elicited by nFlaA, rFlaA, dnFlaA, inhibited following intraperitoneal bacterial challenge. Both protective efficacy carrier protein function retained when conjugated KP O1 OPS. conclude unlike case FlaB glycan, an important epitope induction antibodies.