Humoral and cellular immune response to tick-borne-encephalitis (TBE) vaccination depends on booster doses in patients with Juvenile Idiopathic Arthritis (JIA).

Juvenile Idiopathic Arthritis (JIA) patients living in areas with high prevalence of tick-borne-encephalitis-virus-(TBEV)-infection are recommended for administration of inactivated TBE-vaccination. However, there are serious concerns regarding protective vaccine-induced immune responses against TBEV in immunocompromised patients. The present study aimed to analyze the humoral and cellular immune response to TBE-vaccination in previously TBE-vaccinated JIA patients compared to healthy controls (HC) including investigation of IgG-anti-TBEV avidity, neutralization capacity, cellular reactivity by IFNgamma-ELISPOT and cytokine secretion assays. Similar IgG-anti-TBEV antibody concentrations, neutralization titers and cellular reactivity were found between JIA and HC. The number and the early timing of booster vaccinations after primary vaccination had the most prominent effect on neutralizing antibodies in JIA and on IgG-anti-TBEV concentrations in both JIA and HC. Administration of booster vaccinations made it more likely for JIA patients to have IgG-anti-TBEV concentrations ≥165 VIEU/ml and avidities >60%. TNF-alpha inhibitors had a positive and MTX administration a negative effect on humoral immune responses. In conclusion, irrespective of having JIA or not, vaccinated children showed similar humoral and cellular immunity against TBEV several years after primary TBE-vaccination. However, in JIA, booster vaccinations mounted a significantly higher humoral immune response than in JIA without boosters. Our results highlight the need for timely administration of boosters particularly in JIA. Although immunosuppressive treatment at vaccinations in diagnosed JIA had a negative effect mainly on TBEV-specific cellular immunity, most JIA patients mounted a favorable humoral immune response which was maintained over time. Thus, successful TBE-vaccination seems highly feasible in JIA patients with immunosuppressive regimens.

Differences of IgG antibody avidity after an acellular pertussis (aP) booster in adolescents after a whole cell (wcP) or aP primary vaccination.

Compared to whole cell pertussis (wcP) vaccines, acellular pertussis vaccines (aP) have a better safety profile with lower reactogenicity, although their short and long-term efficacy was found to be slightly lower. Up to now, no established serological parameter to predict long-term protection exists. IgG-anti-pertussis avidity possibly determines the effect of different pertussis vaccines and boosting intervals on long-term immunity. Thus, the avidity of a tetanus-diphtheria-aP booster at 10-14 years was tested in three groups of adolescents who had been previously immunized with either five doses of aP (5aP) at 2, 4, 6, 15-18 months and 5-6 years of age, four doses of aP (4aP) or four doses of wcP (4wcP) at 2, 4, 6 and 15-18 months of age. Relative avidity index (RAI) of IgG-anti-pertussis toxin (PT) and IgG-anti-filamentous-hemagglutinin (FHA) was assessed by an adapted ELISA. RAI of IgG-anti-PT and of IgG-anti-FHA correlated positively with antibody concentrations in the pre-vaccination and in the post-vaccination analysis and significantly increased after adolescent booster with aP in all groups. Pre- and post-vaccination, the proportion of participants with IgG-anti-PT RAI>40% (moderate to high avidity) was significantly lower in the 4wcP group (52.9% and 88.9%) compared to the 5aP group (89.5% and 100.0%). In conclusion, TdaP in adolescence induces an increase of antibody avidity and, thus, is able to enhance the binding-quality of antibodies against pertussis. The study suggests including antibody avidity into serological studies on the humoral response to provide information about the long-term efficacy of the vaccine.

Assessment of IgG avidity against pertussis toxin and filamentous hemagglutinin via an adapted enzyme-linked immunosorbent assay (ELISA) using ammonium thiocyanate.

Antibody avidity, defined as the strength of binding between antibody and antigen, represents a functional measure of affinity maturation of antibodies. Determination of the antibody avidity is usually performed separating high and low avidity antibodies by dissociating agents, but measurement of the antibody avidity in humans is rather complicated, due to the heterogeneity of the antibodies produced in response to complex antigens, e.g. after vaccinations. The purpose of the present study was to evaluate the experimental determinants of the assessment of avidities of IgG antibodies directed against pertussis toxin (IgG-anti-PT) and filamentous hemagglutinin (IgG-anti-FHA) produced after pertussis vaccination using an adapted ELISA and ammonium thiocyanate (NH(4)SCN) as dissociating agent. Our experiments revealed that the results of avidity testing depend very much on experimental conditions and may over- or underestimate the relative avidity of IgG-anti-PT and IgG-anti-FHA antibodies. Whereas in our findings avidity seems to be independent from the initial antibody concentration in a wide range of measures, RAI depends on NH(4)SCN concentration, time of incubation and temperature of the reaction. The presented method allows an accurate measurement of the IgG antibody avidity against both Bordetella pertussis antigens PT and FHA, using NH(4)SCN as chaotropic agent in concentrations lower than 3.0M for 20 min time of incubation at 37 °C. Different experimental conditions in testing pertussis-specific IgG antibody avidity should be considered in interpretation and comparability of data of different studies.

CD4+ and CD8+ mediated cellular immune response to recombinant influenza nucleoprotein.

The stimulatory properties of soluble recombinant influenza nucleoprotein (NP) on purified CD4(+) and CD8(+) T cells from young and elderly individuals were studied. Recombinant influenza NP failed to induce proliferation of resting CD4(+) and CD8(+) T cells in the absence of IL-2. Addition of small amounts of IL-2, however, led to strong proliferation of resting CD4(+) and CD8(+) T cells from young and elderly donors. NP-reactive CD4(+) and CD8(+) T cell lines from both age groups grew equally well under long-term culture conditions. T cell lines raised to live influenza virus could recognize recombinant influenza NP and showed a substantial proliferative response. Stimulation of CD8(+) T cells is presumably due to cross-presentation, as EBV-transformed MHC class I-positive cell lines, which are incapable of antigen processing, stimulated live influenza virus-reactive CD8(+) T cell lines when loaded with NP-derived immunodominant peptides but not following loading with the whole NP molecule. Vaccines containing recombinant influenza NP might confer cross-protective immunity and could therefore be especially useful in cases of major epidemics or pandemics.