Development of cellular immune response after infant pneumococcal conjugate vaccinations

Prevenar®, a seven-valent pneumococcal conjugate vaccine has been registered
for use in a so-called 3+1 vaccination schedule consisting of a three dose
primary series followed by a booster vaccination. It has been introduced in the
Dutch National Immunization Program in April 2006 for vaccination at 2, 3, 4
and 11 months of age.
Prevenar vaccination provides immediate protection against pneumoccocal related
diseases through the induction of functional antibodies, which however only
have a short half-life indicating the need for a memory response. Both the
induction and maintenance of functional serum antibody titres have a cellular
basis which is still poorly understood.
In general, antigens trigger naïve B-cells to expand and differentiate into two
types of affinity matured B-cells: antibody secreting plasma B cells and memory
B-cells. Since plasma cells are unlikely to persist for more than 6-8 weeks
(Gourley TS et al, 2004) maintenance of steady state antibody levels over
periods of years requires a continuous low level of differentiation of memory B
cells into plasma cells. Factors such as recurrent antigen exposure such as
through carriage might be involved in this process.
Prevenar is thought to induce immediate protection through stimulation of
antibody production by polysaccharide specific plasma B cells, sustained
protection is conferred by a memory B cell pool which induces an accelerated
increase in antibody titres during secondary immune responses seen after
re-infection or boosting.
An improved understanding of the immunobiology of the B-cell response to
conjugate vaccines, such as Prevenar, is essential to develop immunization
strategies that provide sustained protection.

Primary objective
To determine the development of the cellular immune response (plasma B cells
and memory B-cells), immediately before and after the booster of the 3+1
Prevenar® vaccination schedule at 11 months of age and before and after the
challenge vaccination at 24 months of age

Secondary objective
To determine development of the immune response by looking at antibody
concentrations, avidity and opsonophagocytoses immediately before and after the
booster of the 3+1 Prevenar® vaccination schedule at 11 months of age and
before and after the challenge vaccination at 24 months of age

Parallel group trial

Group 4 receives a single challenge vaccination with Prevenar® vaccine

All children undergo one blood collection of 8 ml. The burden and risk
associated with the blood collection is low. The children might find the needle
scary and it might be painful (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.
Children in group 4 (N=25) receive a challenge vaccination in order to
stimulate the production of memory cells.
The Pneumococcal vaccination gives protection against invasive pneumococcal
disease (IPD) caused by the 7 pneumococcal vaccine types. It is indicated for
children aged 2-24 months. A vaccination at 24 months of age is a registered
application, although not deemed necessary for protection once the children
have received a 4 dose schedule (at 2, 3, 4 and 11 months of age). It is
expected that the extra vaccination at 24 months of age will not cause any
other side effects then the previous Prevenar® vaccinations.