A Replicating Single-Cycle Adenovirus Vaccine Effective against <i>Clostridium difficile</i>
<i>Clostridium difficile</i> causes nearly 500,000 infections and nearly 30,000 deaths each year in the U.S., which is estimated to cost $4.8 billion. <i>C. difficile</i> infection (CDI) arises from bacteria colonizing the large intestine and releasing two toxins, toxin A (Tc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/3/470 |
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| author | William E. Matchett Stephanie Anguiano-Zarate Goda Baddage Rakitha Malewana Haley Mudrick Melissa Weldy Clayton Evert Alexander Khoruts Michael Sadowsky Michael A. Barry |
| author_facet | William E. Matchett Stephanie Anguiano-Zarate Goda Baddage Rakitha Malewana Haley Mudrick Melissa Weldy Clayton Evert Alexander Khoruts Michael Sadowsky Michael A. Barry |
| author_sort | William E. Matchett |
| collection | DOAJ |
| description | <i>Clostridium difficile</i> causes nearly 500,000 infections and nearly 30,000 deaths each year in the U.S., which is estimated to cost $4.8 billion. <i>C. difficile</i> infection (CDI) arises from bacteria colonizing the large intestine and releasing two toxins, toxin A (TcdA) and toxin B (TcdB). Generating humoral immunity against <i>C. difficile</i>’s toxins provides protection against primary infection and recurrence. Thus, a vaccine may offer the best opportunity for sustained, long-term protection. We developed a novel single-cycle adenovirus (SC-Ad) vaccine against <i>C. difficile</i> expressing the receptor-binding domains from TcdA and TcdB. The single immunization of mice generated sustained toxin-binding antibody responses and protected them from lethal toxin challenge for up to 38 weeks. Immunized Syrian hamsters produced significant toxin-neutralizing antibodies that increased over 36 weeks. Single intramuscular immunization provided complete protection against lethal BI/NAP1/027 spore challenge 45 weeks later. These data suggest that this replicating vaccine may prove useful against CDI in humans. |
| first_indexed | 2024-03-10T16:59:27Z |
| format | Article |
| id | doaj.art-f00be2bc33194d98a768b053726c0cbb |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T16:59:27Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-f00be2bc33194d98a768b053726c0cbb2023-11-20T11:02:23ZengMDPI AGVaccines2076-393X2020-08-018347010.3390/vaccines8030470A Replicating Single-Cycle Adenovirus Vaccine Effective against <i>Clostridium difficile</i>William E. Matchett0Stephanie Anguiano-Zarate1Goda Baddage Rakitha Malewana2Haley Mudrick3Melissa Weldy4Clayton Evert5Alexander Khoruts6Michael Sadowsky7Michael A. Barry8Virology and Gene Therapy (VGT) Graduate Program, Mayo Clinic, Rochester, MN 55905, USAClinical and Translational Science (CTS) Graduate Program, Mayo Clinic, Rochester, MN 55905, USAMayo Summer Undergraduate Research Fellow (SURF), Mayo Clinic, Rochester, MN 55905, USAMolecular Pharmacology and Experimental Therapeutics (MPET) Graduate Program, Mayo Clinic, Rochester, MN 55905, USAInflammatory Bowel Program, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN 55454, USAInflammatory Bowel Program, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN 55454, USAInflammatory Bowel Program, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN 55454, USAInflammatory Bowel Program, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, MN 55454, USADepartment of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55905, USA<i>Clostridium difficile</i> causes nearly 500,000 infections and nearly 30,000 deaths each year in the U.S., which is estimated to cost $4.8 billion. <i>C. difficile</i> infection (CDI) arises from bacteria colonizing the large intestine and releasing two toxins, toxin A (TcdA) and toxin B (TcdB). Generating humoral immunity against <i>C. difficile</i>’s toxins provides protection against primary infection and recurrence. Thus, a vaccine may offer the best opportunity for sustained, long-term protection. We developed a novel single-cycle adenovirus (SC-Ad) vaccine against <i>C. difficile</i> expressing the receptor-binding domains from TcdA and TcdB. The single immunization of mice generated sustained toxin-binding antibody responses and protected them from lethal toxin challenge for up to 38 weeks. Immunized Syrian hamsters produced significant toxin-neutralizing antibodies that increased over 36 weeks. Single intramuscular immunization provided complete protection against lethal BI/NAP1/027 spore challenge 45 weeks later. These data suggest that this replicating vaccine may prove useful against CDI in humans.https://www.mdpi.com/2076-393X/8/3/470Clostridium difficileadenovirussingle-cyclevaccineanimal models |
| spellingShingle | William E. Matchett Stephanie Anguiano-Zarate Goda Baddage Rakitha Malewana Haley Mudrick Melissa Weldy Clayton Evert Alexander Khoruts Michael Sadowsky Michael A. Barry A Replicating Single-Cycle Adenovirus Vaccine Effective against <i>Clostridium difficile</i> Vaccines Clostridium difficile adenovirus single-cycle vaccine animal models |
| title | A Replicating Single-Cycle Adenovirus Vaccine Effective against <i>Clostridium difficile</i> |
| title_full | A Replicating Single-Cycle Adenovirus Vaccine Effective against <i>Clostridium difficile</i> |
| title_fullStr | A Replicating Single-Cycle Adenovirus Vaccine Effective against <i>Clostridium difficile</i> |
| title_full_unstemmed | A Replicating Single-Cycle Adenovirus Vaccine Effective against <i>Clostridium difficile</i> |
| title_short | A Replicating Single-Cycle Adenovirus Vaccine Effective against <i>Clostridium difficile</i> |
| title_sort | replicating single cycle adenovirus vaccine effective against i clostridium difficile i |
| topic | Clostridium difficile adenovirus single-cycle vaccine animal models |
| url | https://www.mdpi.com/2076-393X/8/3/470 |
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