Effect of Milk on the Vaccination Response

Study Overview
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Brief Summary
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Rationale: Oral vaccination is known to induce a systemic immune response as well as an immune response in mucosal tissues, and can therefore serve as a model to study systemic and mucosal immunity. In this study, the oral cholera vaccine Dukoral® was chosen as model vaccine. The kinetics of the immune response and the interaction with a raw milk matrix have been evaluated in a previous, pilot study (NL49042.081.14). Based on the outcomes of this pilot, in this study oral cholera vaccination will be applied to study the support of immunity by raw milk, compared to heat-treated milk. The study design has been optimised based on previous results: study duration is extended and sample size is based on relevant change and known variation in the primary outcome parameters. Infections are an important worldwide cause of death, both in elderly and young children. Therefore, support of immunity could help to reduce the incidence of infections. To screen the potential of specific foods or food ingredients to support immunity, oral vaccination can serve as a model. In a previous study, this model was developed using oral cholera vaccination in human adult volunteers. In that study, raw milk was shown to support the immune response to vaccination. In this follow-up study, the effect of raw milk will be compared with pasteurized and ultra-heat treated (UHT) milk. Objective: To investigate whether pasteurized milk and/or UHT milk are able to enhance the immune response as induced by oral cholera vaccination, in comparison to raw milk and to regular vaccination. Study design: The study is designed as a single-blind randomized controlled trial of 6 weeks. Study population: Healthy subjects of 18-50 years of age. Interventions: 1) Raw milk, obtained from farms that comply to the high quality requirements for production of raw milk, and that has been screened according to the safety criteria for raw milk; 2) commercially available full-fat UHT milk; 3) commercially available full-fat pasteurized milk.

Official Title
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MOSAIC-2: Effect of Raw Milk on the Immune Response Upon Cholera Vaccination

Conditions
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Infection

Intervention / Treatment
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* Biological: cholera vaccination
* Other: raw milk
* Other: pasteurized milk
* Other: UHT milk


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-50 yr Signed informed consent Availability of internet connection Male or female Willing to stop blood donation at the blood bank during the study period Exclusion Criteria: Currently participating in another clinical trial Previous Cholera, Salmonella, or E. coli vaccination Tonsillectomy Acute gastroenteritis in the past 2 months Use of antibiotics in the past 2 months Hypersensitivity to the vaccine, to formaldehyde or to any of the excipients (sodium salts) Pregnancy or lactating Not willing to drink raw milk Allergic to milk or lactose-intolerant Disease of GI tract, liver, gall bladder, kidneys, thyroid gland Immune-compromised Use of immunosuppressive drugs Drug abuse, and not willing/able to stop this during the study Excessive alcohol usage (men: >4 consumptions/day or >20 consumptions/week; women: >3 consumptions/day or >15 consumptions/week)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>Regular cholera vaccination | Biological: cholera vaccination<br>* Oral cholera vaccination on day 0 and day 14<br>* Other names: Dukoral;|
| Active Comparator: Raw milk<br>Cholera vaccination - raw milk | Biological: cholera vaccination<br>* Oral cholera vaccination on day 0 and day 14<br>* Other names: Dukoral;Other: raw milk<br>* raw milk<br>|
| Active Comparator: Pasteurized milk<br>Cholera vaccination - pasteurized milk | Biological: cholera vaccination<br>* Oral cholera vaccination on day 0 and day 14<br>* Other names: Dukoral;Other: pasteurized milk<br>* pasteurized milk<br>|
| Active Comparator: UHT milk<br>Cholera vaccination - UHT milk | Biological: cholera vaccination<br>* Oral cholera vaccination on day 0 and day 14<br>* Other names: Dukoral;Other: UHT milk<br>* UHT milk<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cholera toxin-specific IgA and IgG antibody level in serum as a marker of the vaccination response |  | baseline and day 14, 28, 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the cholera toxin-specific IgA and IgG antibody level in nasal wash as a marker of the vaccination response |  | baseline and day 14, 28, 42 | 
| Change in the cholera toxin-specific IgA and IgG antibody level in saliva as a marker of the vaccination response |  | baseline and day 14, 28, 42 | 
| Change in the cholera toxin-specific IgA antibody level in feces as a marker of the vaccination response |  | baseline and day 14, 28, 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunity, vaccination, milk