De role of Cytomegalovirus-infection on T-cell dynamics after influenza vaccination in elderly

Infection with Cytomegalovirus (CMV) in healthy individuals does not cause
clinical symptoms. However, it is associated with enhanced immunosenescence
(aging of the immune system) and therefore can lead to decreased efficiency of
(influenza) vaccines. The mechanism behind this impaired immune response to new
antigens in CMV-infected elderly is unknown. CMV has a great influence on the
composition of the T cell compartment in elderly. It induces great numbers of
memory cells, which might have a competing function with memory cells to other
antigens, such as for influenza. In this study, we want to test the hypothesis
that the production rate and/or death rate of T cells after an influenza
vaccination is lower in CMV-positive compared to CMV-negative elderly.

To investigate the effect of cytomegalovirus(CMV)-infection on the production
rate and death rate of T cells after influenza vaccination in elderly.

The study is longitudinal and consist of two phases; (1) CMV reactivation and
screening study and (2) the heavy water study. Phase (1) consists of one blood-
and saliva collection on the day of inclusion. First we include 40
participants. In the case that we cannot select the 10 participant for phase 2
of the study from these 40 participants, we will include another 20
participants (thus 60 in total). Phase (2) consists of (A) temporarily drinking
of heavy water, (B) an seasonal influenza vaccination and (C) frequent
collection of blood and urine samples. In total, the study will take around 2
years.

Intervention: In phase 2 of the study, the ten participants will receive the
seasonal influenza vaccination of 2016/2017.

Invasive procedures: One blood sample and one saliva sample will be collected
from the participants in phase 1. In phase 2, blood (8 times, in total 816 ml
in 1 year in phase 2) and urine (13 times, of which 6 by mail) will be
collected frequently. A short questionnaire (about the health status since last
blood collection) will also be performed by the researcher during each visit of
the participant to the hospital.

Imposed behaviour: Only applicable for participants of phase 2 to measure T
cell dynamics; drinking the start bolus of heavy water of circa 350 ml on day
0, followed by a daily dose of about 60 ml heavy water for 5 weeks.

Participants of phase 1 of the study will visit the UMC Utrecht 1 time during
which blood and saliva will be collected. The selected 10 participants of
phase 2 will visit the UMC Utrecht another 10 times of which 1 visit (visit 3)
will take a whole day. In one visit (visit 1) the influenza vaccination will be
given Participants will drink heavy water for 5 weeks, which can cause on the
first day (because of the greater amount of heavy water) some nausea and/or
dizziness. During the other 5 weeks, the participants will drink daily a
smaller amount of heavy water.

In the 10 visits blood will be collected (30,5 to 111,5 ml per time) of in
total 874 ml in approximately 1 year, which is within the policy of Sanquin
blood bank. During 7 visits, and 7 times by mail, a urine sample will also be
handed in (13 times in total).. In the case that a participant is suffering
from influenza-like-illness, a nose and throat swab will be taken during a home
visit to identify influenza-infection

The risks of venepuncture, the registered influenza vaccine and drinking of
heavy water is minimal. Although the physical burden of the study is minimal,
there is some personal burden for participants; the time and energy that
participants should invest for the hospital visits and blood collections and
the traveling to and from the hospital.