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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Typhoid Vaccination
• Intervention / Treatment: Drug: Vivotif Typhoid Oral Vaccine

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Universtiy of Maryland, Baltimore, Center for Vaccine Development and Global Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccination, Colonoscopy; 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; 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).; Other Names: Ty21a Typhoid Oral Vaccine
Experimental: Colonoscopy, Vacciniation, Colonoscopy; 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; 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).; Other Names: Ty21a Typhoid Oral Vaccine
No Intervention: Colonoscopy Without Vaccination; 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?

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

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2013
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: May 29, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 31, 2019

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Salmonella Infections; Typhoid Fever; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: HP-00056321

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No