CVD 37000: Immunity and Microbiome Studies at Intestinal and Systemic Sites in Ty21a Vaccinated Adults

Study Overview
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Brief Summary
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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.

Conditions
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Typhoid Vaccination

Intervention / Treatment
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* Drug: Vivotif Typhoid Oral Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years and older Undergoing colonoscopy for screening or surveillance for colorectal cancer at the University of Maryland Provide written informed consent prior to initiation of any study procedures Healthy, as defined by considered fit to undergo outpatient elective colonoscopy by the referring health care provider 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 immune-deficiency disorders such as Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS) leukemia, lymphoma, or cancers immune suppressive medications or treatments, such as corticosteroids or radiation Receipt of any other vaccine two weeks prior to receipt of Ty21a Positive urine pregnancy test (HCG) prior to colonoscopy or vaccination

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccination, Colonoscopy<br>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. | Drug: Vivotif Typhoid Oral Vaccine<br>* 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).<br>* Other names: Ty21a Typhoid Oral Vaccine;|
| Experimental: Colonoscopy, Vacciniation, Colonoscopy<br>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. | Drug: Vivotif Typhoid Oral Vaccine<br>* 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).<br>* Other names: Ty21a Typhoid Oral Vaccine;|
| No Intervention: Colonoscopy Without Vaccination<br>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). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 |