Induction of Gut Permeability by an Oral Vaccine

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Brief Title

Induction of Gut Permeability by an Oral Vaccine

Official Title

Induction of Gut Permeability by an Oral Vaccine

Brief Summary

      This study evaluates the effect of an oral typhoid vaccine on disruption of the intestinal
      barrier and response of the immune system. Intestinal and whole-body responses will be
      measured in all participants before and after the vaccine.

Detailed Description

      The licensed Ty21a vaccine strain of S. enterica Typhi is routinely used by travelers to
      countries where typhoid is common. It is not known whether the vaccine causes measurable
      changes in intestinal permeability and whether changes in permeability are correlated with
      the magnitude of the vaccine response. In the current study, gut permeability will be
      measured in participants at baseline and after an aspirin challenge, which is known to
      disrupt intestinal permeability, and after the first, second, and fourth doses of a the Ty21a
      vaccine. Intestinal permeability will be measured using a three-sugar absorption test
      composed of lactulose, mannitol, and sucralose and by several plasma markers. Vaccine
      response will be measured by quantitating T cells and newly developed IgG-or IgA-secreting
      plasma cells specific for Ty21a.

Study Phase

Early Phase 1

Study Type


Primary Outcome

Change in intestinal permeability

Secondary Outcome

 Antibody response to typhoid vaccination


Intestinal Permeability


Vivotif Typhoid Oral Vaccine

Study Arms / Comparison Groups

 Single group
Description:  All participants will receive the vaccine and aspirin.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

December 4, 2019

Completion Date

September 30, 2022

Primary Completion Date

January 31, 2022

Eligibility Criteria

        Inclusion Criteria:

          -  Body Mass Index (BMI) 18.5 - 29.9 kg/m2

        Exclusion Criteria:

          -  Has HIV/AIDS or another disease that affects the immune system

          -  Has any kind of cancer

          -  Decline to take an HIV blood test

          -  Blood pressure greater than or equal to 140/90 mmhg

          -  Pregnant or lactating women

          -  Refusal to take a pregnancy test prior to the study

          -  Refusal to use a method of birth control during the study

          -  Allergy to vaccine components, i.e. Thimerosal and enteric-coated capsules

          -  Allergy to oral typhoid vaccine

          -  Allergy to aspirin

          -  Daily use of blood thinners

          -  Use of anti-inflammatory medications, i.e. nonsteroidal anti-inflammatory drugs
             (NSAID), aspirin, 3 or more times per month

          -  Use of sulfonamides or antibiotics in the past 30 days

          -  Use of anti-hypertensive drugs, i.e. beta blockers, diuretics, calcium channel

          -  Use of anti-malaria drugs, i.e. Mefloquine, chloroquine, and proguanil

          -  Use of drugs that affect the immune system, i.e. immunosuppressants, immune-modifying
             drugs, corticosteroids, i.e. cortisone, prednisone, methylprednisolone, for 2 weeks or

          -  Is taking cancer treatment with radiation or drugs

          -  Greater than ten years residence in a typhoid-endemic area

          -  Receipt of typhoid vaccine in the last 5 years

          -  Receipt of any vaccine two weeks prior to receipt of Ty21a vaccine

          -  Individuals at increased risk of developing complications from a live, bacterial

          -  History of typhoid fever

          -  History of primary immune deficiency or autoimmune disease

          -  History of acute or chronic gastrointestinal (GI) disorder, i.e. Crohn's disease,
             irritable bowel syndrome, gastric ulcer

          -  Diarrheal illness (defined as passing 3 or more abnormally loose or watery stool in a
             24 hour period) or persistent vomiting 2 weeks prior to the study

          -  History of bleeding disorder, including bleeding from the GI tract

          -  History of chronic illnesses, i.e. diabetes, cardiovascular disease, cancer,
             gastrointestinal malabsorption or inflammatory diseases, kidney disease, autoimmune
             disorders, HIV, liver disease, including hepatitis B and C.

          -  Asthma if taking medication on a daily basis

          -  Recent surgery (within 3 months)

          -  History of GI surgery

          -  Recent hospitalization (within 3 months)

          -  Acute febrile illness (within 2 weeks)

          -  Unwillingness to discontinue consumption of artificial sweeteners in foods or drinks,
             i.e. sport drinks, coconut water, "diet" drinks and foods (possibly containing

          -  Not having at least one arm vein suitable for blood drawing

          -  Unwilling or uncomfortable with blood draws seven times in 29 days

          -  Regular blood or blood product donation and refusal to suspend donation

          -  Current participation in another research study

          -  Unable to fast for 12-16 hours




18 Years - 49 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers


Danielle Lemay, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party


Study Sponsor

USDA, Western Human Nutrition Research Center

Study Sponsor

Danielle Lemay, PhD, Principal Investigator, USDA, ARS, Western Human Nutrition Research Center

Verification Date

March 2022