Optimizing primary vaccination schedule for premature infants

The National Immunization Program (NIP) aims to protect all individuals and the
population at large against the target diseases. The current *one size fits
all* NIP schedule may not provide optimal protection to preterm infants, a
situation that is highly undesirable, both from a societal perspective, because
of the negative impact on herd-immunity, and for reasons of individual health
risks with infection in this vulnerable population. A targeted and personalized
approach to vaccination of the 15.000 preterm infants born annually, could
improve overall NIP effectiveness. Yet, optimal timing and dosing for this
group is currently unknown. Immunogenicity studies in preterm infants and
clinical testing of alternative vaccination schedules is critical to optimize
their protection against vaccine preventable diseases.

Primary Objectives:
1) To determine immunogenicity of NIP vaccines in preterm infants when
vaccinated according to the current Dutch NIP schedule and with rotavirus
vaccine following the RIVAR study.
2) To unravel the mechanism of immature host responses and interaction with
gestational age (GA)
3) To propose alternative, better-adapted vaccination schedules with respect
to number and timing of doses for preterm infants, based on the immunogenicity
findings

Secondary Objective(s):
1) To determine the tolerability of NIP vaccines and rotavirus vaccine in
preterm infants as measured by the occurrence of vaccine side effects.
2) To determine the timelines of NIP vaccines in preterm infants under the
current NIP schedule.
3) To explore the possible cellular immune mechanisms for the impaired vaccine
response in preterm infants
4) To explore possible immunological differences between preterm infants
delivered by caesarion section or by natural vaginal delivery and between
breath fed versus formula fed infants.

Observational study nested within the non- WMO RIVAR (Risk-group Infant
Vaccination Against Rotavirus) study. All RIVAR participants are eligible for
inclusion. PRIEMA participants will undergo blood sampling.

The PRIEMA study can only be performed in preterm infants.
Blood sampling from infants participating in the immunogenicity study will be
performed by venapuncture and combined with routine medically indicated blood
sampling whenever possible. In all other circumstances a trained research nurse
or medical doctor will perform venapuncture during routine clinic or study
home-visits. Analgestic cream will be locally applied to the infants skin prior
to the procedure. A maximum of two attempts to collect blood will be executed
per scheduled measurement time-point. The procedure of blood sampling by
venapuncture is of extremely low risk to the infant and of minimal discomfort.
The stool samples collected by parents of participating infants will be taken
from soiled diapers and are therefore non-invasive. Checking the dates of
vaccinations and weight from the "green book", will not take more then 5
minutes.
Therefore, the risk and burden of participation in this study are minimal as
compared to the potential value of the study.