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Bioinformatic and experimental identification and characterization of Clostridioides difficile lipoproteins as potential vaccine candidates
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Bioinformatic and experimental identification and characterization of Clostridioides difficile lipoproteins as potential vaccine candidates
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Journal Article
Bioinformatic and experimental identification and characterization of Clostridioides difficile lipoproteins as potential vaccine candidates
2025
Overview
Treatment options for
infection are limited, with very high rates of recurrence. Active vaccination provides an attractive opportunity to prevent
infection (CDI) and recurrence. In a search for potential surface-exposed antigens involved in
colonization, two putative lipoproteins, designated LP1 and LP2, were identified from
R20291.
Lipoprotein sequences were aligned, analyzed, and evaluated for their immune properties. The antigenic characteristics of both LP1 and LP2 were assessed in silico and in a mouse model of immunization and CDI.
Multiple sequence alignments showed that the lipoprotein sequences were highly conserved among various ribotypes.
analysis predicted that LP1 and LP2 possess cytotoxic T-lymphocyte, helper T-lymphocyte, and B-cell epitopes with antigenic and immunogenic properties. Immune simulation provided insights into the ability of LP1 and LP2 to stimulate humoral and cellular immune responses. These properties were further examined in a mouse model of immunization and CDI. After three immunizations at 12-day intervals, significant amounts of IgG and IgA antibodies were detected in sera and feces. LP1 and LP2 immunizations provided mice with intermediate and higher levels of protection, respectively, against R20291 infection, and significantly reduced
spore and toxin levels in feces. Furthermore, anti-LP1 and anti-LP2 sera significantly inhibited adhesion of R20291 vegetative cells to HCT-8 gut epithelial cells.
These results indicate that both lipoproteins play a significant role in
adhesion and that LP1 and LP2 are promising immunogens for preventing
colonization.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
/ Animals
/ Antibodies, Bacterial - blood
/ Antibodies, Bacterial - immunology
/ Antigens, Bacterial - immunology
/ Bacterial Proteins - genetics
/ Bacterial Proteins - immunology
/ Bacterial Vaccines - immunology
/ Clostridioides difficile - immunology
/ Clostridium Infections - immunology
/ Clostridium Infections - microbiology
/ Clostridium Infections - prevention & control
/ Computational Biology - methods
/ Datasets
/ Epitopes
/ Feces
/ Female
/ Genomes
/ Humans
/ Immune response (cell-mediated)
/ Mice
/ Peptides
/ Proteins
/ Toxins
/ Trees
/ vaccine
/ Vaccines
