Serologic evaluation of Hepatitis B vaccination (Infanrix hexa)

Since 1st March 2003, hepatitis B virus (HBV) vaccine is offered in the Dutch
National Immunisation Programme to children with one or two parents born in a
HBV endemic country (this is about 18% of each birth cohort). Initially, HBV
vaccine was offered as a separate injection. . Since 1st April 2006 it is
offered as a combination vaccine (Infanrix hexa), so that pneumococcal vaccine
could be introduced without increasing the number of injections to three.

There is some information in the literature, that giving pneumococcal
vaccination at the same time could reduce the immunogenicity of the HBV
vaccination (Scheifele, Vaccine 2006, Tichmann-Schumann, PIDJ 2005, Knuf et
al., Vaccine 2006). A reduced immune response was the reason that the European
Agency for the Evaluation of Medicinal Products (EMEA) withdrew the license for
a vaccine that is very similar to Infanrix hexa (Hexavac; EMEA 297369/2005).

It has also been suggested that the Hib response after Infanrix vaccination
could be reduced as a result of giving pneumococcal vaccine at the same time
(Goldblatt, PIDJ, in press). Also the pertussis and pneumococcal response may
be reduced following combined administration.

To assess the immune response is important, since an insufficient response
would mean that children in the target group for HBV vaccination are
insufficiently protected.

The director of the Centre for Infectious Disease control suggested that
changes in the immunisation programme should be carefully evaluated, including
serological evaluation. In addition, the Dutch Health Council advised in 2003
after recommending introduction of HBV vaccination for the target group, that
this should be evaluated after three years.

The aim of the study is to evaluate whether the HBV serological response to
Infanrix hexa vaccination, after administration according to the Dutch National
Immunisation Programme, is sufficient according to World Health Organisation
(WHO) standrads.

Additional objectives are
- to assess whether the responses to the Hib, pertussis and pneumococcal
components are sufficient after combined administration of Infanrix hexa and
pneumococcal vaccine.
- To assess the acceptability of HBV vaccination.

The serological evaluation will be carried out using similar methods as are
currently employed for the serological evaluation of children of HBV carrier
mothers. Parents of eligible children will be invited at the child health
clinic (consultatiebureau) to take part. When agreeing to take part, they are
asked to bring their child to a clinic, 4 to 6 weeks after the last (fourth)
Infanrix hexa vaccination, so that blood can be taken through venapuncture.
Travel costs will be reimbursed (participants receive a 'strippenkaart'). Blood
will be sent to RIVM, with subsequent serological tests carried out at UMCU
(anti-Hbs, HBsag) and at RIVM (other serological tests). HBsAg will only be
determined for children with a anti-HBs titer <100 IU/ml.

The serological tests regarding the additional study questions (Hib, pertussis
and pneumococcal disease) will be carried out once funding is available. Hence,
the results of these tests will not be communicated with participants' parents.

Results re HBV will be sent to the participant's child health clinic. In case
of a sufficient serological response, the results will also be sent directly to
the parents. In case of insufficient response, the results will be communicated
trhough the child health clinic. Then, a new series of vaccinations will be
offered, with a subsequent serological test. In case of HBV carriage, this will
be communicated with the parents during a child health clinic visit. In this
case, the general practitioner will also be informed, with the advice to refer
the child to a specialist.

To assess acceptability, questions regarding the HBV vaccination and other
vaccinations will be asked in questionnaire, to parents of participants.

Participants will be asked to give blood once (through venapuncture). When the
HBV response is insufficient, additional HBV vaccinations with a subsequent new
serological evaluation, will be offered.