Effect of Milk on the Vaccination Response (MOSAIC-2)

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

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.

Study Overview

• Status: Completed
• Conditions: Infection
• Intervention / Treatment: Biological: cholera vaccination; Other: raw milk; Other: pasteurized milk; Other: UHT milk

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Ede, Netherlands, 6718 ZB
    • NIZO food research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control group; Regular cholera vaccination	Biological: cholera vaccination; Oral cholera vaccination on day 0 and day 14; Other Names: Dukoral
ACTIVE_COMPARATOR: Raw milk; Cholera vaccination - raw milk	Biological: cholera vaccination; Oral cholera vaccination on day 0 and day 14; Other Names: Dukoral; Other: raw milk; raw milk
ACTIVE_COMPARATOR: Pasteurized milk; Cholera vaccination - pasteurized milk	Biological: cholera vaccination; Oral cholera vaccination on day 0 and day 14; Other Names: Dukoral; Other: pasteurized milk; pasteurized milk
ACTIVE_COMPARATOR: UHT milk; Cholera vaccination - UHT milk	Biological: cholera vaccination; Oral cholera vaccination on day 0 and day 14; Other Names: Dukoral; Other: UHT milk; UHT milk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Time Frame
Change in the expression of intestinal and mucosal homing markers on IgA and IgG antibody-secreting B cells in peripheral blood, measured by flow cytometry, as markers of the route of modulation of the vaccination response	baseline and day 14
Cholera toxin-specific T cell proliferation as marker of modulation of the vaccination response	baseline and day 14

Collaborators and Investigators

• Sponsor: NIZO Food Research
• Collaborators: FrieslandCampina

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ACTUAL): December 1, 2017

Study Registration Dates

• First Submitted: September 29, 2016
• First Submitted That Met QC Criteria: October 3, 2016
• First Posted (ESTIMATE): October 5, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 5, 2018
• Last Update Submitted That Met QC Criteria: September 3, 2018
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: vaccination; immunity; milk
• Other Study ID Numbers: NL56906.081.16

Plan for Individual participant data (IPD)

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