Immunological response after early extra and regular MMR immunization; 10 years follow-up

The latest epidemic lasted from May 2013 until March 2014. The Outbreak
Management Team (OMT) of the RIVM at that time advised to administer an early
extra measles, mumps and rubella (MMR-0) immunization during this outbreak, to
protect children below one year of age in areas with lower immunization
coverage (less than 90%) and thus with higher risk of exposure to measles
virus. To monitor the long term immunological effects of this outbreak measure,
a clinical study was performed (NL45616.094.13/IIV-273). In this study,
children who received the MMR-0 vaccination between 6 and 12 months of age in
addition to the regular vaccination at 14 months of age were compared to a
control group of children who only received the regular vaccination at 14
months of age. Most children who received an MMR-0 vaccination between 6-12
months of age showed a measles antibody response and were regarded to be
protected during the measles epidemic. A small percentage of the children who
received MMR-0 between 6 and 8 months of age (~12%) had measles IgG levels
below the threshold of protection (<=0.12 IU/ml) at 14 months of age prior to
MMR-1 vaccination. After the regular MMR-1 vaccination at 14 months of age, all
children had gained protective antibody levels, both in the MMR-0 group and in
the regular MMR-1 group. Three years later, measles antibody levels dropped
below the protective threshold in 11% of the 6-8 months MMR-0 vaccinated
children, while all of the 9-12 months MMR-0 vaccinated children and children
who only received the regular MMR-1 dose still had protective measles levels.
At 6-7 years of age, this percentage had increased to 68%. Among the children
who received an MMR-0 dose between 9 and 12 months of age and the children of
the control group who only received their regular MMR-1 at 14 months of age,
21% and 11% respectively, had dropped below the threshold of protection
[preliminary data].

Primary Objective:
- To assess the effect of MMR-0 vaccination on the humoral immunity against
measles 2 years (+/- 2 months) after MMR-2 vaccination.

Secondary Objective(s):
- Determine the effect of MMR-0 vaccination on the humoral immunity against
mumps and rubella 2 years (+/- 2 months) after MMR-2 vaccination.

Exploratory Objective(s):
- Determine the effect of MMR-0 vaccination on the functionality and isotype
distribution of antibodies against measles 2 years (+/- 2 months) after MMR-2
vaccination.

In this follow-up study, a single small blood sample will be collected by
finger-stick, of children who previously were immunized with an MMR-0
vaccination between 6-12 months of age, and children 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 at 2 years (+/- 2 months) post MMR-2
vaccination. Parents can perform the finger-stick on their child themselves and
mail the blood sample to the RIVM. If parents do not feel comfortable
performing the finger-stick themselves, an alternative can be arranged.
Furthermore, a digital questionnaire is filled out with questions about the
health of the child and other vaccinations.

In this study, we follow the children who previously participated in the EMI
study (children who received an MMR-0 vaccination were compared to children who
only received the regular MMR-1 vaccination, NL45616.094.13/IIV-273 and
NL69434.100.19 / IIV-411) or in the BMR-nul questionnaire study. 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 2 years (+/- 2 months) after MMR-2
vaccination in MMR-0 vaccinated children and regular MMR-1 vaccinated children.
We already have immunological data from these children from our previous
studies to compare these results with, and therefore they are the only possible
participants.