MOSAIC-2 Study: MOdel to Study upper Airway Immunity upon Cholera vaccination

Oral vaccination is known to induce a systemic immune response as well as a
weak immune response in the upper airways, and can therefore serve as a model
to study systemic and upper airway immunity. 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 (upper airway)
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.

To investigate whether raw milk, pasteurized milk or ultra-heat treated (UHT)
milk is able to enhance the systemic immune response as induced by oral cholera
vaccination, in comparison to regular vaccination. Oral vaccination can also
induce an immune response in the upper airways. Therefore, the effect of milk
on the upper airway response after vaccination will also be analysed.

Four groups of 27 healthy adult volunteers (total n=108) will be vaccinated
with the oral cholera vaccine Dukoral®. The vaccine is given on day 0 and day
14 of the study. One group will receive the vaccine in the regular sodium
carbonate buffer. The other groups will receive the vaccine in a matrix of raw
milk, UHT milk or pasteurized milk, respectively. At baseline, and 14, 28 and
42 days after start of the vaccination, the immune response will be measured in
blood, saliva, nasal wash and feces.

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 (a.o. presence of specific pathogens); 2) commercially
available full-fat UHT milk; 3) commercially available full-fat pasteurized
milk

The participants will visit the study location once for screening and 4 times
for vaccination and/or sample collection. At those 4 time points, 40-60 mL of
blood will be drawn (total amount 240 mL). At all time points, a nasal wash
will be performed. At 4 time points, saliva and fecal samples will be collected.
At 2 time points, the participants will receive a dosage of the vaccine.
Dukoral® is a registered vaccine, consisting of heat-killed and formalin-killed
Vibrio cholerae plus recombinant cholera toxin subunit B. The vaccine can be
safely used for adults and for children above the age of 2 yr. The vaccination
has a low risk of side effects, and the side effects are mainly mild. One group
will receive the vaccine in a matrix of raw milk. Raw milk has a potential risk
of containing pathogens that can result in gastrointestinal disease. By
selecting farms that comply to strict quality criteria, and by screening the
milk for specific pathogens, the risk of subsequent infection is considered
very limited. In the previous MOSAIC study (NL49042.081.14) no adverse events
were observed related to the consumption of raw milk.
Two groups will receive the vaccine in a matrix of full-fat pasteurized or UHT
milk. This does not results in extra risks.
Side effects occurring during the study will be registered by a short daily
online survey. If serious side effects occur, the study doctor will be
consulted.
The study participants will have no direct benefit from the study.