Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against <i>Clostridioides difficile</i> Infection
Background/Objectives: <i>Clostridioides difficile</i> is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for <i>C. difficile</i> infection (C...
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MDPI AG
2024-12-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/13/1/21 |
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| author | Shaohui Wang Joshua Heuler Jessica Bullock Junling Qin Soumyadeep Chakraborty Agbendeh Lubem Nathaniel Shifeng Wang Xingmin Sun |
| author_facet | Shaohui Wang Joshua Heuler Jessica Bullock Junling Qin Soumyadeep Chakraborty Agbendeh Lubem Nathaniel Shifeng Wang Xingmin Sun |
| author_sort | Shaohui Wang |
| collection | DOAJ |
| description | Background/Objectives: <i>Clostridioides difficile</i> is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for <i>C. difficile</i> infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed <i>C. difficile</i> cell wall protein, plays an important role in the bacterium’s adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice. Methods: we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection. Results: Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced <i>C. difficile</i> spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of <i>C. difficile</i> vegetative cells to HCT8 cells. Conclusions: Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice. |
| format | Article |
| id | doaj-art-2d0cd640ed024a9389fa32970141556a |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-2d0cd640ed024a9389fa32970141556a2025-01-24T13:51:41ZengMDPI AGVaccines2076-393X2024-12-011312110.3390/vaccines13010021Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against <i>Clostridioides difficile</i> InfectionShaohui Wang0Joshua Heuler1Jessica Bullock2Junling Qin3Soumyadeep Chakraborty4Agbendeh Lubem Nathaniel5Shifeng Wang6Xingmin Sun7Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USADepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USADepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USADepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USADepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USADepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USADepartment of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 33620, USADepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USABackground/Objectives: <i>Clostridioides difficile</i> is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for <i>C. difficile</i> infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed <i>C. difficile</i> cell wall protein, plays an important role in the bacterium’s adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice. Methods: we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection. Results: Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced <i>C. difficile</i> spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of <i>C. difficile</i> vegetative cells to HCT8 cells. Conclusions: Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice.https://www.mdpi.com/2076-393X/13/1/21<i>Clostridioides difficile</i> infection (CDI)colonizationCwp2vaccine |
| spellingShingle | Shaohui Wang Joshua Heuler Jessica Bullock Junling Qin Soumyadeep Chakraborty Agbendeh Lubem Nathaniel Shifeng Wang Xingmin Sun Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against <i>Clostridioides difficile</i> Infection Vaccines <i>Clostridioides difficile</i> infection (CDI) colonization Cwp2 vaccine |
| title | Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against <i>Clostridioides difficile</i> Infection |
| title_full | Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against <i>Clostridioides difficile</i> Infection |
| title_fullStr | Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against <i>Clostridioides difficile</i> Infection |
| title_full_unstemmed | Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against <i>Clostridioides difficile</i> Infection |
| title_short | Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against <i>Clostridioides difficile</i> Infection |
| title_sort | cell wall protein 2 as a vaccine candidate protects mice against i clostridioides difficile i infection |
| topic | <i>Clostridioides difficile</i> infection (CDI) colonization Cwp2 vaccine |
| url | https://www.mdpi.com/2076-393X/13/1/21 |
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