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.
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 Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
10
One capsule is swallowed on alternate days, e.g. days 15, 17, 19, and 21, for a total of 4 capsules.
Three tablets (325 mg aspirin in each tablet or 975 mg total) are swallowed on days 2 and 3.
USDA, ARS, Western Human Nutrition Research Center
Davis, California, United States
Change in intestinal permeability
Measurement of sugar (lactulose, D-mannitol, and sucralose) excretion in urine.
Time frame: Day 1, 3, 16, 18, and 22
Antibody response to typhoid vaccination
Measurement of Typhi-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) plasma cells in peripheral blood using the antibody in lymphocyte supernatant assay.
Time frame: Day 1, 18, 22, 24, and 29
T-cell response to typhoid vaccination
Measurement of vaccine-specific cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) T-cells in peripheral blood mononuclear cells.
Time frame: Day 1, 22, and 29
Change in markers of inflammation
Measurement of plasma cytokines, chemokines, and acute phase proteins by a multiplex immunoassay.
Time frame: Day 1, 3, 16, 18, 22, and 24
Change in intestinal fatty acid binding protein (iFABP)
Measurement of plasma iFABP.
Time frame: Day 1, 3, 16, 18, and 22
Change in D-lactate
Measurement of plasma D-lactate.
Time frame: Day 1, 3, 16, 18, and 22
Change in diamine oxidase
Measurement of plasma diamine oxidase.
Time frame: Day 1, 3, 16, 18, and 22
Change in lipopolysaccharide binding protein (LBP)
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Measurement of plasma LBP.
Time frame: Day 1, 3, 16, 18, and 22
Change in citrulline
Measurement of plasma citrulline.
Time frame: Day 1, 3, 16, 18, and 22