Characteristics of immune memory 10–15 years after primary hepatitis B vaccination

Background and aims: The definition of immune memory after hepatitis B vaccination is still under debate. Therefore, we analysed hepatitis B surface antigen (HBsAg)-specific memory in more detail by investigating the kinetics of humoral and cellular responses after hepatitis B booster vaccination. Methods: The anti-HBs kinetics of 23 individuals with anti-HBs titres below 10 IU/I, who had been vaccinated 10-15 years ago, was monitored at day 0, 3, 7,14 and 28 after booster vaccination. HBsAg-specific IFN gamma- and IL5-secreting cells in enriched CD4(+) fraction were measured at day 0, 7 and 28 post-booster by enzyme-linked immunospot assay (ELISpot). Results: 22 of 23 subjects showed similar anti-HBs kinetic curves, including 3 of 4 subjects who did not reach anti-HBs titres of 10 IU/I. The steep anti-HBs increase started between day 3 and 7 and peaked around day 14. A plateau or only minimal changes were visible between day 14 and 28. 17.4% of subjects showed pre-booster cellular responses, and this rate had increased to 47.8% and 56.5% after 7 and 28 days, respectively. The kinetic patterns of T cell responses differed considerably among subjects. A dominance of Th2 responses (IL5 secretion) over Th1 responses (IFN gamma secretion) could be observed. Conclusions: The presence of B cell memory could be shown by a typical anamnestic anti-HBs response curve after a booster dose in all but one individual. In contrast, T cell responses to booster vaccination, which occurred in approximately 50% of participants, were rather heterogeneous. (C) 2015 Elsevier Ltd. All rights reserved

Markers of Protection in Children and Adolescents Six to Fourteen Years After Primary Hepatitis B Vaccination in Real Life

Background: Not many data are available on long-term immunity against hepatitis B (HB) for children vaccinated under real-life conditions. Methods: Two hundred and thirty-two children and adolescents vaccinated 6-14 years earlier in pediatric practices were examined for conditions of vaccination and markers of protection as anti-HBs, anamnestic response to a booster dose and cell-mediated immunity. Results: Fifty-six percent of the participants were vaccinated according to the German vaccination recommendations (group 1). In 44.0% (group 2), these recommendations were not followed. Anti-HBs concentrations of >= 10 IU/L were found in 53.1% of group 1 and 45.1% of group 2 participants. A booster dose resulted in 91 of 99 participants in having an anamnestic response, in 3 (5.9%) of group 1 and 5 (10.4%) of group 2 anti-HBs remained below 10 IU/L. In group 1, postbooster anti-HBs concentration was inversely correlated with time since the last vaccination. Cellular immune responses were seen in only 5% of revaccinated individuals before the booster, increasing to 30% thereafter. Conclusions: Under real-life conditions about half of vaccinees have lost protecting antibodies 6-14 years after vaccination in infancy, but in approximately 90% of them, immune memory was demonstrated. However, as memory may wane, revaccination at a time when boostability is still present might be considered

Dissociations in the effects of beta2-adrenergic receptor agonists on cAMP formation and superoxide production in human neutrophils: Support for the concept of functional selectivity

In neutrophils, activation of the beta2-adrenergic receptor (beta2AR), a Gs-coupled receptor, inhibits inflammatory responses, which could be therapeutically exploited. The aim of this study was to evaluate the effects of various beta2AR ligands on adenosine-3',5'-cyclic monophosphate (cAMP) accumulation and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced superoxide anion (O2*-) production in human neutrophils and to probe the concept of ligand-specific receptor conformations (also referred to as functional selectivity or biased signaling) in a native cell system. cAMP concentration was determined by HPLC/tandem mass spectrometry, and O2*- formation was assessed by superoxide dismutase-inhibitable reduction of ferricytochrome c. beta2AR agonists were generally more potent in inhibiting fMLP-induced O2*- production than in stimulating cAMP accumulation. (-)-Ephedrine and dichloroisoproterenol were devoid of any agonistic activity in the cAMP assay, but partially inhibited fMLP-induced O2*- production. Moreover, (-)-adrenaline was equiefficacious in both assays whereas the efficacy of salbutamol was more than two-fold higher in the O2*- assay. In contrast to the agonists, the effects of beta2AR antagonists were comparable between the two parameters on neutrophils. Differences between the data from neutrophils and recombinant test systems were observed for the beta2AR agonists as well as for the beta2AR antagonists. Lastly, we obtained no evidence for an involvement of protein kinase A in the inhibition of fMLP-induced O2*- production after beta2AR-stimulation, although, in principle, cAMP-increasing substances can inhibit O2*- production. Taken together, our data corroborate the concept of ligand-specific receptor conformations with unique signaling capabilities and suggest that the beta2AR inhibits O2*- production in a cAMP-independent manner