MOSAIC study:
MOdel to Study upper Airway Immunity upon Cholera vaccination

Airway infections are an important worldwide cause of death, both in elderly
and young children. Upper airway infections are a risk factor for the
development of lower airway infections, which are often more severe. Therefore,
support of upper airway immunity could help to reduce the incidence of lower
airway infection.
To screen the potential of specific foods or food ingredients to support airway
immunity in young children is not feasible. Therefore, an alternative human
model was identified. Oral vaccination is known to induce a weak immune
response in the upper airways, and can therefore serve as a model to study
upper airway immunity. The oral cholera vaccine Dukoral® was chosen as model
vaccine, for 3 reasons: its availability as registered vaccine, its safety, and
the availability of information on the kinetics of the immune response. In this
study, oral cholera vaccination will be applied in human adult volunteers, and
used as a model to study the support of upper airway immunity by raw milk.
Milk, and especially raw milk, is known to contain many different bioactive
compounds. Several of these compounds have been shown to be involved in the
protection against infection and in the support of immunity. Notably, raw milk
consumption is inversely associated with the occurrence of asthma, upper
respiratory tract infection and otitis media. Pasteurization and homogenization
can harm these compounds and reduce the bioactivity of milk. Therefore, in this
study, the effect of raw milk will be evaluated on the immune response to oral
cholera vaccination.

To investigate whether raw milk is able to enhance the upper airway immune
response as induced by oral cholera vaccination.

Three groups of 14 healthy adult volunteers (total n=42) 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. One group will receive the vaccine in a matrix of raw milk.
One group will receive the vaccine in a matrix of raw milk and keep every sip
in the mouth for 30 seconds, to have prolonged exposure to raw milk and to the
vaccine. At baseline, and 7, 14, 18 and 28 days after start of the vaccination,
the immune response will be measured in blood, saliva, nasal wash and feces.

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).

The participants will visit the study location 6 times. At 5 time points, 40-60
mL of blood will be drawn (total amount 260 mL). At 6 time points, a nasal wash
will be performed. At 10 time points, saliva will be collected. At 5 time
points, 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. Two
groups 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.
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.