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This is an open-label, non-randomized study. The purpose of this study is to better understand how vaccines against typhoid fever affect the normal immune system and bacteria in the intestine. Patients having standard-of-care colonoscopies will be divided into 3 groups:
Group 1: Vivotif typhoid vaccination then colonoscopy; Group 2: Colonoscopy, then Vivotif typhoid vaccination, then follow-up colonoscopy; Group 3: Colonoscopy without vaccination.
The Vivotif typhoid vaccine used in this study is licensed by the Food and Drug Administration (FDA) for travelers to developing countries. Volunteers will be asked to donate tissue, blood, saliva and stool samples for studying how the body responds to the typhoid vaccine.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vaccination, Colonoscopy | Experimental | Individuals receive immunization with Vivotif typhoid vaccine prior to routine colonoscopy examination. During colonoscopy, small bowel biopsies will be obtained to examine immune responses and microbiota at the mucosal level; brushings will also be obtained. |
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| Colonoscopy, Vacciniation, Colonoscopy | Experimental | Individuals receive immunization with Vivotif typhoid vaccine after initial colonoscopy exam and specimen collection and prior to a routine follow up colonoscopy examination during which additional specimens will be collected. |
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| Colonoscopy Without Vaccination | No Intervention | Individuals do not receive immunization but consent to collection of specimens during colonoscopy. The specimens to be collected in all three groups include stool, saliva, and small bowel biopsies (terminal ileum). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vivotif Typhoid Oral Vaccine | Drug | The 4 doses (1 capsule each) will be administered on alternate days, e.g., days 0, 2, 4, and 7 (± 1 day) under the supervision of the study coordinator(s). |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Responders | Percentage of responders by cytokine production (Interferon-gamma (IFN-gamma) or Tumor Necrosis Factor-alpha (TNF-α)) by mass cytometry or flow cytometry. Responders will be defined as those volunteers showing increases post-immunization of >0.1% of positive CD8+ cells for IFN-gamma or TNF-α over baseline (pre-immunization) values.) or Tumor Necrosis Factor-alpha (TNF-α)) by mass cytometry or flow cytometry. | approximately 5 years |
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Inclusion Criteria:
Exclusion Criteria:
Pregnancy or nursing mother
Known coagulopathy or bleeding disorder preventing mucosal biopsy
History of Crohn's disease or ulcerative colitis
Surgical removal of the ileocecal valve or any part of the small or large intestine
Allergic reaction to oral typhoid vaccine in the past
Immunosuppression from illness or treatment, including
Receipt of any other vaccine two weeks prior to receipt of Ty21a
Positive urine pregnancy test (HCG) prior to colonoscopy or vaccination
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universtiy of Maryland, Baltimore, Center for Vaccine Development and Global Health | Baltimore | Maryland | 21201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33874975 | Derived | Booth JS, Goldberg E, Patil SA, Barnes RS, Greenwald BD, Sztein MB. Age-dependency of terminal ileum tissue resident memory T cell responsiveness profiles to S. Typhi following oral Ty21a immunization in humans. Immun Ageing. 2021 Apr 19;18(1):19. doi: 10.1186/s12979-021-00227-y. | |
| 32098623 | Derived | Booth JS, Goldberg E, Barnes RS, Greenwald BD, Sztein MB. Oral typhoid vaccine Ty21a elicits antigen-specific resident memory CD4+ T cells in the human terminal ileum lamina propria and epithelial compartments. J Transl Med. 2020 Feb 25;18(1):102. doi: 10.1186/s12967-020-02263-6. |
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Volunteers who choose to take part in this study will receive the licensed FDA approved Oral Typhoid Vaccine (Vivotif). Volunteers also have the possibility of being a control participant who will not be vaccinated.
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