Immunological effect of early extra MMR immunization in infants between 6 and 12 months of age in an outbreak setting

In 2013/2014 a measles outbreak occurred in the Netherlands. The Dutch Ministry
of Health has decided to offer infants between 6 and 12 months of age, who live
in the measles outbreak area, an early extra MMR (MMR-0) immunization. This is
to protect these young children otherwise susceptible for measles infection,
due to earlier loss of transplacentally acquired measles antibodies in infants,
especially those born from mothers that have acquired measles immunity through
immunization instead of through natural infection. While this early measles
immunization has been shown to be effective in outbreak situations, the
acquired humoral immune response for these children is expected to be different
from children immunized at 14 months of age, which is the regular age of
primary measles immunization. Early MMR immunization may also affect immunity
to the other two components in the combination vaccine, mumps and rubella. In
addition, possible interference with the generation of an immune response
against the other vaccines of the Nation Immunisation Program for infants
(DTaP-IPV-Hib-HepB, Pneumo and MenC) is anticipated.

The preliminary results show differences in the antibodies of children who had
the early extra BMR-0 vaccination compared to children in the control group.
These differences are more clear at one year post BMR-1. For this reason an
extra visit at 3 years post BMR-1 is added to the study, to look form the
long-term effects.

Main:
To assess the effect of an early extra measles immunization between 6
and 12 months of age on the development of humoral and cell-mediated
immunity against measles following routine MMR immunization at 14
months of age.

Secundary:
Determine effect of early extra measles immunization on the
immunogenicity against other infant vaccines of the NIP

Determine the influence of maternal measles, mumps and rubella antibodies on
the infants'
immune response to MMR immunization

Determine the rate of measles (neutralizing) antibody decline between 6
weeks, 1 year and 3 years after routine MMR immunization at 14 months of age

a controlled open parallel group trial

Group 1: children having received MMR-0. Blood collection at 14 months of age +
immunization with MMR-1 and MenC, bloodcollection 7-9 days post MMR-1 (subset),
6 weeks post MMR-1, 1 year and 3 years post MMR-1

Group 2: children NOT having received MMR-0. Blood collection at 14 months of
age + immunization with MMR-1 and MenC, bloodcollection 7-9 days post MMR-1
(subset), 6 weeks post MMR-1, 1 year and 3 years post MMR-1

This study is designed to monitor the effects of an early extra MMR-0
immunization in children 6 to 12 months of age in a measles outbreak area, with
the aim to protect these vulnerable infants against measles at an earlier age.
Actual administration of this early extra MMR-0 immunization will be performed
before study entry.
The routine 14 months of age NIP immunizations MMR-1 and MenC will be
administered during the first home-visit to allow pre-immunization blood
sampling.

The study will gain insight into the immunological changes following an extra
early MMR-0 immunization, which will help us to optimize our approach to
potential future outbreaks as to optimally protect Dutch infants. The children
are eligible for this early extra MMR-0 immunization and are therefore the only
possible participants. Additional recruitment of the control group can be done
in children <14 months of age, participating in the NIP. The children have no
direct benefit from participating in the study. The MMR-1 and MenC
immunizations that are given during the first home-visit are part of the
standard NIP and are thus not changed, despite that these immunizations will be
given at home instead of during the regular well-baby clinic visits as part of
the NIP. Blood collections can give a small bruise, which will resolve within a
few days. There are no other risks.