Vaccine safety controversies and the future of vaccination programs

In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine "scares" continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.     

Hepatitis B immunisation induces higher antibody and memory Th2 responses in new-borns than in adults

New-borns raise limited antibody responses to most T cell-dependent antigens but little is known about neonatal T lymphocyte responses to vaccines. In this study, we compared the immune response induced by the hepatitis B vaccine in new-borns and nai;ve adults. Infants produced markedly higher serum anti-hepatitis B surface (HBs) antibody titres than adults. This was not associated with greater HBs Ag-specific Th2 cytokine responses but with lower primary IFN-gamma responses. At 1 year, the infant memory response to HBs Ag was characterised by higher Th2 responses than those of adults. We conclude that neonatal antibody and T cell responses to hepatitis B vaccine differ from those induced in adults.     

Co-administration of CpG oligonucleotides enhances the late affinity maturation process of human anti-hepatitis B vaccine response

We assessed the avidity maturation process elicited by human immunization with alum-adsorbed HBsAg alone or with a novel adjuvant containing CpG motifs (CpG 7909). Mean avidity indexes and distribution of low- and high-avidity anti-HBs indicated that avidity maturation essentially takes place late after priming. CpG 7909 markedly enhanced this affinity maturation process, increasing the pool of high-avidity antibodies. The influence of CpG 7909 was antigen-specific, isotype-specific and distinct from the influence on anti-HBs production, as avidity did not correlate with anti-HBs IgG titers. This is the first demonstration that a novel human adjuvant may induce antibodies with higher antigen-binding affinity.     

The measurement of effort-reward imbalance at work: European comparisons

Using comparative data from five countries, this study investigates the psychometric properties of the effort-reward imbalance (ERI) at work model. In this model, chronic work-related stress is identified as non-reciprocity or imbalance between high efforts spent and low rewards received. Health-adverse effects of this imbalance were documented in several prospective and cross-sectional investigations. The internal consistency, discriminant validity and factorial structure of 'effort', 'reward', and 'overcommitment' scales are evaluated, using confirmatory factor analysis. Moreover, content (or external) validity is explored with respect to a measure of self-reported health. Data for the analysis is derived from epidemiologic studies conducted in five European countries: the Somstress Study (Belgium; n = 3796), the GAZEL-Cohort Study (France; n = 10,174), the WOLF-Norrland Study (Sweden; n = 960), the Whitehall II Study (UK; n = 3697) and the Public Transport Employees Study (Germany; n = 316). Internal consistency of the scales was satisfactory in all samples, and the factorial structure of the scales was consistently confirmed (all goodness of fit measures were > 0.92). Moreover, in 12 of 14 analyses, significantly elevated odds ratios of poor health were observed in employees scoring high on the ERI scales. In conclusion, a psychometrically well-justified measure of work-related stress (ERI) grounded in sociological theory is available for comparative socioepidemiologic investigations. In the light of the importance of work for adult health such investigations are crucial in advanced societies within and beyond Europe.     

Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants

Several mechanisms have been suggested as mediating the inhibitory influence of maternal antibodies (MatAb) on infant responses. This inhibition is B cell determinant-specific, depends on the ratio between MatAb titers at the time of immunization and the dose of vaccine antigen, and leaves infant T cell responses largely unaffected. Neutralization of vaccine replication or FcgammaRIIB-mediated inhibitory signalling to infant B cells would not account for these characteristics. In contrast, determinant-specific masking of B cell epitopes and APC uptake of MatAb:vaccine antigen immune complexes, followed by antigen processing and presentation, explain the pattern of pre-clinical and clinical responses to infant vaccines. This allows the definition of the main determinants of the influence of MatAb on infant immunity.