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Vaccination has reduced the disease burden of vaccine-preventable diseases. However, the extent to which seasonal cycles of immunity could influence vaccine-induced immunity is not well understood. A national cross-sectional serosurveillance study performed in the Netherlands (Pienter-2) yielded data to investigate whether season of vaccination was associated with antibody responses induced by DT-IPV (diphtheria, tetanus and poliomyelitis), MMR (measles, mumps and rubella) and meningococcus C (MenC) vaccines in children. In total, 434 children met the inclusion criteria to study DT-IPV immunity, 811 for MMR and 311 for MenC. Differences in log(antibody levels) by season of vaccination were investigated with linear multivariable regression analyses. Seroconversion rates varied according to season of vaccination for rubella (90% of autumn-vaccinated childrenvs.99% of winter-vaccinated had concentrations above cut-off levels). Summer-vaccinated boys showed a slower decline of tetanus antibodies (6% per month), in comparison with winter-vaccinated boys. In conclusion, season of vaccination showed little association with immunological protection. However, a number of associations were seen with aP-value of about 0.03; and adding data from a just-completed nationwide serological study might add more power to the current study. Further immunological and longitudinal investigations could help understand the mechanisms of seasonal influence in vaccine-induced responses.

The most important neutralizing and protective antibodies against Measles virus (MeV) are directed against the hemagglutinin protein (MeV-H). To define the MeV binding domains recognized by human antibodies a set of 10 non-redundant MeV-H-specific monoclonal antibodies (mabs) was used to block their binding in a competition ELISA. Sera from both naturally infected and vaccinated individuals showed similar competition patterns. Two distinct domains were identified as the main target of human antibodies. One domain corresponded to the region of the previously described hemagglutinin noose epitope (HNE, aa 380-400) [35], which is recognized by hemagglutination-inhibiting, neutralizing and protective mabs. The second region is defined by a mab with strong neutralizing but weak hemagglutination-inhibiting activity. Mabs with a strong neutralizing capacity with respect to wild-type viruses seemed to displace more human antibodies than those with a weaker neutralizing activity. Human antibodies seem to react more weakly with the hemagglutinin regions that bind the CD46 and the fusion protein and more strongly with the putative CD150 binding site and the top loops of beta-sheet 2 and 3 of the hemagglutinin.

We assessed antibodies to the capsular polysaccharide of Haemophilus influenzae type b (HibPS) in the Dutch population a few years after a mass vaccination against H. influenzae (Hib) was begun. We observed sharp declines in the geometric mean titer (GMT) and the prevalence of HibPS antibodies at levels ofor =0.15 microg/mL in children who had received 4 doses of vaccine: from 8.65 microg/mL (prevalence, 99.4%) after 0-2 months to 0.8 microg/mL (prevalence, 83.3%) after 27-29 months. In adult groups, both the prevalence of HibPS antibodies and the GMT declined significantly with increasing age but remained high (prevalence,or =83.7%; GMT, 0.73or = microg/mL). We conclude that the overall immunity in the Dutch population seems satisfactory. We draw our conclusions from the current serosurveillance study and from the sharp decline in invasive Hib disease noted after the introduction of vaccination. The key questions for the future are (1) whether Hib and cross-reacting organisms will circulate sufficiently to provide natural reexposure, and (2) how long memory immunity will persist after vaccination without reexposure.

We assessed the tetanus immunity of the general Dutch population and of religious groups refusing vaccination by means of population-based study to evaluate the effect of tetanus vaccination. More than 95% of those born after the introduction of routine vaccination had tetanus antitoxin levels above the minimum protective level. After the sixth vaccination, a fall in tetanus antitoxin levels occurred. Nevertheless, immunisation in accordance with the routine programme most likely induces protection for much longer than two decades. Not only many members of religious groups who refuse vaccination, but also many adults born before the introduction of vaccination lack tetanus immunity. These cohorts might benefit most from (re)vaccination.

In 2006/2007 a large serum bank was established by means of a cross-sectional population-based study. This serum bank will be used to evaluate the Dutch national immunisation programme (NIP) by serosurveillance and additional immunological and epidemiological research. In this paper we describe the design of this population-based cross-sectional serosurvey and report the participation rates as well as general characteristics of the study population. A similar serum bank was collected in 1995/1996. Dutch inhabitants (aged 0-79 years, men and women) were invited from 40 municipalities throughout the country and also from eight additional municipalities known with low vaccination coverage (LVC). An oversampling of the migrant population was performed. Blood samples were obtained from all participants accompanied with extensive information on demographic and epidemiological data, such as vaccination history, risk factors and travelling. In addition, sociodemographic data are available from individuals who declined to participate (non-response survey). Overall 33% of all invitees were included in this study. The serum bank comprises 6386 sera in the nationwide sample including the extra sample of immigrants (n=646) and 1518 sera from the LVC municipalities. The sera will be analysed for antibodies against all NI P antigens but will also be used for other infectious diseases research. Results of this second serosurveillance study will contribute to the discussion whether it is needed to reconsider the schedule and/or the vaccine components of the current National Immunisation Programme.

The immunity to vaccine-preventable diseases included in the Dutch immunisation programme in the general population and among orthodox reformed individuals who refuse vaccination was assessed. The programme induces good protection. However, a large proportion of adults lacks diphtheria and tetanus immunity. Measles, mumps and rubella seroprevalence was somewhat lower among vaccinated compared to unvaccinated cohorts. The prevalence of HibPS antibodies declined during 2.5 years after the fourth vaccination. However, protection occurs also by memory immunity. Herd immunity is sufficient among the general population, but not among orthodox reformed individuals. Immunosurveillance is an efficient way to evaluate the effects of immunisation programmes and identify risk groups for infection.

A two-dose mass vaccination programme with a combined vaccine against measles, mumps and rubella (MMR) was adopted in the Netherlands in 1987, replacing the selective schoolgirl vaccination strategy introduced in 1974. To obtain insight into the effect of mass vaccination and the population's immunity, the antibody levels against rubella were studied in the general Dutch population and in religious groups refusing vaccination. In the national sample, we observed a high prevalence (96·5%) for rubella antibodies in vaccinated cohorts as well as in the older unvaccinated cohorts. No indications of rapidly waning immunity after vaccination were found. There are indications of low virus circulation in the last few years. The very high seroprevalence in women at childbearing age is consistent with the few reported cases of congenital rubella syndrome (CRS) at present. However, individuals in the age group of 1–9 years who are not vaccinated for religious or other reasons have a considerably lower seroprevalence and thus there is a potential risk of a CRS outbreak in the future.