ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicNew Generation Bacterial Vaccines Based on Immune Correlates of ProtectionView all 4 articles
Bioinformatic and experimental identification and characterization of Clostridioides difficile lipoproteins as potential vaccine candidates
Provisionally accepted
- 1University of South Florida, Tampa, United States
- 2Virginia Tech Virginia Agricultural Experiment Station, Blacksburg, United States
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Treatment options for C. difficile infection are limited with very high rates of recurrence. Active vaccination provides an attractive opportunity to prevent C. difficile infection (CDI) and recurrence. In a search for potential surface-exposed antigens against C. difficile colonization, two putative lipoproteins designated as LP1 and LP2 were identified from C. difficile R20291. Multiple sequence alignments showed that the lipoprotein sequences were highly conserved among various ribotypes. In-silico analysis predicted that LP1 and LP2 possesses cytotoxic T-lymphocyte, helper T-lymphocyte and B-cell epitopes with antigenic and immunogenic properties. Immune simulation provided insight into the capability of LP1 and LP2 for stimulating humoral and cellular immune responses. These properties were further evaluated in the mouse model of immunization and C. difficile infection (CDI). After immunization of mice thrice at an interval of 12 days, significant amounts of IgG and IgA antibodies were detected in the sera and feces. LP1 and LP2 immunizations provided mice intermediate and higher protection, respectively against R20291 infection, and significantly reduced C. difficile spore and toxin levels in mouse feces. Furthermore, anti-LP1 and anti-LP2 sera significantly inhibited adhesion of R20291 vegetative cells to the gut epithelium cells HCT-8, indicating that both lipoproteins played a significant role in C. difficile adhesion. In conclusion, LP1 and LP2 are potential immunogens against C. difficile colonization.
Keywords: Clostridioides difficile, lipoprotein, colonization, Vaccine, Epitope analysis, Mousemodel
Received: 19 Jun 2025; Accepted: 20 Nov 2025.
Copyright: © 2025 Chakraborty, Heuler, Wang, Roy and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xingmin Sun, sun5@health.usf.edu
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