Effect of Milk on the Vaccination Response

NCT02924246 — Not applicable, Completed, 108 participants, NIZO Food Research

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

Registry	NCT02924246, acronym MOSAIC-2
Status	Completed
Phase	Not applicable
Study type	Interventional; randomized, parallel, masking: single, prevention
Enrollment	108 (Actual)
Sponsor	NIZO Food Research (Other); collaborators: FrieslandCampina
Conditions	Infection
Interventions	cholera vaccination, raw milk, pasteurized milk, UHT milk (Biological, other)
Dates	start 2016-08-01, primary completion 2016-12-01, completion 2017-12-01, first posted 2016-10-05, last updated 2018-09-05
Locations	1 site in Netherlands

-Summary

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.

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+Arms and interventions

Arm	Type	Interventions	Description
Control group	Placebo comparator	Biological: cholera vaccination	Regular cholera vaccination
Raw milk	Active comparator	Biological: cholera vaccination; Other: raw milk	Cholera vaccination - raw milk
Pasteurized milk	Active comparator	Biological: cholera vaccination; Other: pasteurized milk	Cholera vaccination - pasteurized milk
UHT milk	Active comparator	Biological: cholera vaccination; Other: UHT milk	Cholera vaccination - UHT milk

cholera vaccination (Biological), also known as Dukoral: Oral cholera vaccination on day 0 and day 14
raw milk (Other): raw milk
pasteurized milk (Other): pasteurized milk
UHT milk (Other): UHT milk

+Outcome measures

Primary outcomes

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 outcomes

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 outcomes

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]

+Eligibility

Sex: All, ages: 18 Years to 50 Years, accepts healthy volunteers

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)

+Locations (1)

Facility	City	Country	Status
NIZO food research	Ede	Netherlands

+Investigators

Els van Hoffen, PhD, Principal investigator, NIZO Food Research