Novel Chimeric Protein Vaccines Against Clostridium difficile Infection
Clostridium difficile infection (CDI) is the leading cause of world-wide nosocomial acquired diarrhea in adults. Active vaccination is generally accepted as a logical and cost-effective approach to prevent CDI. In this paper, we have generated two novel chimeric proteins; one designated Tcd169, comp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02440/full |
| _version_ | 1811228932447404032 |
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| author | Shaohui Wang Yuanguo Wang Ying Cai Ciaran P. Kelly Xingmin Sun |
| author_facet | Shaohui Wang Yuanguo Wang Ying Cai Ciaran P. Kelly Xingmin Sun |
| author_sort | Shaohui Wang |
| collection | DOAJ |
| description | Clostridium difficile infection (CDI) is the leading cause of world-wide nosocomial acquired diarrhea in adults. Active vaccination is generally accepted as a logical and cost-effective approach to prevent CDI. In this paper, we have generated two novel chimeric proteins; one designated Tcd169, comprised of the glucosyltransferase domain (GT), the cysteine proteinase domain (CPD), and receptor binding domain (RBD) of TcdB, and the RBD of TcdA; the other designated Tcd169FI, which contains Salmonella typhimurium flagellin (sFliC) and Tcd169. Both proteins were expressed in and purified from Bacillus megaterium. Point mutations were made in the GT (W102A, D288N) and CPD (C698) of TcdB to ensure that Tcd169 and Tcd169FI were atoxic. Immunization with Tcd169 or Tcd169Fl induced protective immunity against TcdA/TcdB challenge through intraperitoneal injection, also provided mice full protection against infection with a hyper-virulent C. difficile strain (BI/NAP1/027). In addition, inclusion of sFlic in the fusion protein (Tcd169Fl) enhanced its protective immunity against toxin challenge, reduced C. difficile numbers in feces from Tcd169Fl-immunized mice infected C. difficile. Our data show that Tcd169 and Tcd169FI fusion proteins may represent alternative vaccine candidates against CDI. |
| first_indexed | 2024-04-12T10:05:33Z |
| format | Article |
| id | doaj.art-9b8971bea03849c09f1fdd02fb6e6beb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T10:05:33Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9b8971bea03849c09f1fdd02fb6e6beb2022-12-22T03:37:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-10-01910.3389/fimmu.2018.02440412792Novel Chimeric Protein Vaccines Against Clostridium difficile InfectionShaohui Wang0Yuanguo Wang1Ying Cai2Ciaran P. Kelly3Xingmin Sun4Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesDivision of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United StatesDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesClostridium difficile infection (CDI) is the leading cause of world-wide nosocomial acquired diarrhea in adults. Active vaccination is generally accepted as a logical and cost-effective approach to prevent CDI. In this paper, we have generated two novel chimeric proteins; one designated Tcd169, comprised of the glucosyltransferase domain (GT), the cysteine proteinase domain (CPD), and receptor binding domain (RBD) of TcdB, and the RBD of TcdA; the other designated Tcd169FI, which contains Salmonella typhimurium flagellin (sFliC) and Tcd169. Both proteins were expressed in and purified from Bacillus megaterium. Point mutations were made in the GT (W102A, D288N) and CPD (C698) of TcdB to ensure that Tcd169 and Tcd169FI were atoxic. Immunization with Tcd169 or Tcd169Fl induced protective immunity against TcdA/TcdB challenge through intraperitoneal injection, also provided mice full protection against infection with a hyper-virulent C. difficile strain (BI/NAP1/027). In addition, inclusion of sFlic in the fusion protein (Tcd169Fl) enhanced its protective immunity against toxin challenge, reduced C. difficile numbers in feces from Tcd169Fl-immunized mice infected C. difficile. Our data show that Tcd169 and Tcd169FI fusion proteins may represent alternative vaccine candidates against CDI.https://www.frontiersin.org/article/10.3389/fimmu.2018.02440/fullClostridium difficile infectionchimeric proteinvaccineSalmonella typhimurium flagellinimmunization |
| spellingShingle | Shaohui Wang Yuanguo Wang Ying Cai Ciaran P. Kelly Xingmin Sun Novel Chimeric Protein Vaccines Against Clostridium difficile Infection Frontiers in Immunology Clostridium difficile infection chimeric protein vaccine Salmonella typhimurium flagellin immunization |
| title | Novel Chimeric Protein Vaccines Against Clostridium difficile Infection |
| title_full | Novel Chimeric Protein Vaccines Against Clostridium difficile Infection |
| title_fullStr | Novel Chimeric Protein Vaccines Against Clostridium difficile Infection |
| title_full_unstemmed | Novel Chimeric Protein Vaccines Against Clostridium difficile Infection |
| title_short | Novel Chimeric Protein Vaccines Against Clostridium difficile Infection |
| title_sort | novel chimeric protein vaccines against clostridium difficile infection |
| topic | Clostridium difficile infection chimeric protein vaccine Salmonella typhimurium flagellin immunization |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02440/full |
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