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The O-glycan is essential for the induction of protective antibodies against lethal infection by flagella A-bearing Pseudomonas aeruginosa.
Choi, Myeongjin; Shridhar, Surekha; Fox, Heather; Luo, Kun; Amin, Mohammed N; Tennant, Sharon M; Simon, Raphael; Cross, Alan S.
Afiliação
  • Choi M; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Shridhar S; Korea Institute of Toxicology, Daejeon, Republic of Korea.
  • Fox H; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Luo K; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Amin MN; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Tennant SM; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Simon R; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
  • Cross AS; Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Infect Immun ; 92(3): e0042723, 2024 Mar 12.
Article em En | MEDLINE | ID: mdl-38391207
ABSTRACT
To address the problem of increased antimicrobial resistance, we developed a glycoconjugate vaccine comprised of O-polysaccharides (OPS) of the four most prevalent serotypes of Klebsiella pneumoniae (KP) linked to recombinant flagellin types A and B (rFlaA and rFlaB) of Pseudomonas aeruginosa (PA). Flagellin is the major subunit of the flagellar filament. Flagella A and B, essential virulence factors for PA, are glycosylated with different glycans. We previously reported that while both rFlaA and rFlaB were highly immunogenic, only the rFlaB antisera reduced PA motility and protected mice from lethal PA infection in a mouse model of thermal injury. Since recombinant flagellin is not glycosylated, we examined the possibility that the glycan on native FlaA (nFlaA) might be critical to functional immune responses. We compared the ability of nFlaA to that of native, deglycosylated FlaA (dnFlaA) to induce functionally active antisera. O glycan was removed from nFlaA with trifluoromethanesulfonic acid. Despite the similar high-titered anti-FlaA antibody levels elicited by nFlaA, rFlaA, and dnFlaA, only the nFlaA antisera inhibited PA motility and protected mice following lethal intraperitoneal bacterial challenge. Both the protective efficacy and carrier protein function of nFlaA were retained when conjugated to KP O1 OPS. We conclude that unlike the case with FlaB O glycan, the FlaA glycan is an important epitope for the induction of functionally active anti-FlaA antibodies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pseudomonas aeruginosa / Flagelina Limite: Animals Idioma: En Revista: Infect Immun Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pseudomonas aeruginosa / Flagelina Limite: Animals Idioma: En Revista: Infect Immun Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos