Immunological response after early extra and regular MMR immunization; 6 years follow-up

From May 2013 until March 2014, a measles epidemic occurred in the Netherlands.
During this epidemic, the Dutch Ministry of Health decided to offer infants
between 6 and 12 months of age, living in the measles outbreak area, an early
extra MMR (MMR-0) immunization. We previously investigated the immunological
response to early vaccination in a cohort of these children up to 4 years of
age (NL45616.094.13/IIV-273). The first outcome was that all children who
received an early extra MMR-0 vaccination between 6-12 months of age showed a
measles antibody response. A large part of these children had protective
measles levels (<=0.12 IU/ml [1, 2]) at the age of 14 months. These children
were protected during the measles epidemic. After the regular MMR-1 vaccination
at 14 months of age, almost all children had protective levels (both in the
early extra MMR-0 group as in the regular MMR-1 group). Three years later in
part of the early extra MMR-0 vaccinated children measles antibody levels
dropped below the protective threshold, while all regular MMR-1 vaccinated
children still had protective measles levels. This steeper decline of measles
antibody levels will be monitored in the current study. We will measure further
decline in measles specific (functional) antibody concentration and the
proportion of children with antibodies below the cut-off for clinical
protection 6 years after the MMR-1 vaccination.

Primary Objective:
To assess the effect of early extra measles immunization on the humoral
immunity against measles 6 years after MMR-1 at 14 months of age

Secondary Objective(s):
•Determine the effect of early extra measles immunization on the immunity
against mumps and rubella 6 years after MMR-1 at 14 months of age
•Determine the effect of early extra measles immunization on the immunity
against other NIP vaccines 6 years after MMR-1 at 14 months of age

Additional follow-up of a controlled open parallel group trial of children who
were previously included in a study on the immunological effects of early extra
MMR-0

In this follow-up study, a single blood sample will be collected, by finger
stick, of children who previously were immunized with an early extra MMR-0 and
the regular MMR-1 at 14 months of age, and infants of a control group who only
received the regular MMR-1 at 14 months of age. Blood sampling through a
finger-stick will be performed during a home visit at 6 years post MMR-1 (±6
months). Alternatively, if preferred by the parents, they can perform the
finger-stick on their child and send in the blood.

In this study, we follow the children who previously participated in the EMI
study (children who received an extra early MMR-0 vaccination where compared to
children who only received the regular MMR-1 vaccination,
NL45616.094.13/IIV-273). The children have no direct benefit from participating
in the study. Blood collection will be done using a finger-stick, which poses
no risk. The follow-up will gain insight in the antibody levels at 6 years
after MMR-1 in early extra MMR-0 vaccinated children and regular MMR-1
vaccinated children. We already have immunological data from these children
from our previous study to compare these results with, and therefore they are
the only possible participants.