Development of humoral and cellular immune response in infants after pneumococcal conjugate vaccinations with Synflorix® or Prevenar-13®

Streptococcus pneumonia (SP) is an important cause of morbidity and mortality
worldwide, with the highest incidence of disease among children < 2 years of
age. Streptococcus pneumonia consisting of > 90 known different serotypes, of
which a limited number of about 20 serotypes are known to cause invasive
pneumococcal disease (IPD).

Prevenar®, a seven-valent pneumococcal conjugate vaccine (PCV7) was first
introduced in the Netherlands immunization program (NIP) for children born
after April 2006. It confers protection against serotypes 4, 6B, 9V, 14, 18C,
19F and 23F (see figure 1). It has been introduced in the NIP for vaccination
at 2, 3, 4 and 11 months of age. Recently in 2009, two new vaccines were
registered, which can in due time replace PCV7 in the NIP. All children born
after March 2011 will receive Synflorix®, a ten-valent pneumococcal conjugate
vaccine (PCV10) which confers protection against three additional serotypes.
Prevenar-13®, a thirteen-valent pneumococcal conjugate vaccine (PCV13) confers
protection against another three extra serotypes, but is not implemented in the
NIP.

The current study in combination with our previous KOKKI (cellular
immunogenicity after PCV7 vaccination) and PIM (comparison of 4 different PCV13
vaccination schedules based on humoral immunogenicity) study can give input to
the Health Council (HC) on the best vaccination strategy for pneumococcal
vaccination. The outcomes of this trial will provide data on the humoral and
cellular immune response of PCV10 and PCV13.

Primary: To compare immunogenicity (humoral and cellular) induced by PCV10 and
PCV13 after the booster dose of a complete vaccination series (3+1, the current
NIP schedule)

Secondary:
To compare immunogenicity (humoral) induced by PCV10 and PCV13 at 5, 8, 11 and
12 months of a complete vaccination series (3+1, the current NIP schedule)

To investigate the possible influence of the pneumococcal vaccination on the
serological responses of other vaccine components of the NIP which are
administered simultaneously in the other limb (DTaP-Hib)

A controlled randomized parallel group trial with 2 groups (see figure 2 and
table 1).

• Group 1 PCV13
o Divided in group 1a and 1b; 33 infants per group

• Group 2 PCV10
o Divided in group 2a and 2b; 33 infants per group

Group 1 and 2 are split in sub groups in order to reduce the burden of the 8 ml
blood samples. Randomization will be done within group 1 and within group 2.

One blood collection of 8 ml (2x 4 ml tubes). The burden and risk is considered
low.
The children might find the needle scary and it might be painful but only for a
few seconds. A local anaesthetic (Emla® crème, Astra Zeneca) may be used to
minimize pain. Blood collection could result in a small bruise at the location
of injection, which will disappear within a few days.
Group 1; one heel/finger stick sampling, group 2: 3-4 heel/finger sticks
sampling. The burden and risk is considered low.

For group 2 (PCV10 group), the children themselves have no direct benefit in
participating in this trial. The trial is aimed to study the immune response
after 3+1 PCV10 or PCV13 vaccinations. These children, who have followed the
Dutch NIP, are the only possible children that can participate in the trial.
Visits will take 10-30 minutes each (depending on the type of blood collection
and whether a questionnaire is taken).

Children in group 1 will receive PCV13 vaccinations. The side effects of these
vaccinations are expected to be equal to the side effects of PCV10 (which the
children would have received as part of the NIP). They will however receive
these vaccinations at home to reduce the burden. These children will benefit
from the added protection of the three extra serotypes which are not present in
the PCV10 vaccination. These children are the only possible study group, since
they are eligible for the Dutch NIP. Visits will take maximum 30 minutes each.