Seropersistence of TBE virus antibodies 10 years after first booster vaccination and response to a second booster vaccination with FSME-IMMUN 0.5mL in adults.

Tick-borne encephalitis (TBE) is a viral disease that can have a severe acute clinical course and considerable long-term morbidity. As there is no causal treatment currently available for TBE, vaccination is the only way to combat the disease in endemic areas. The studies presented here were conducted to obtain prospective long-term TBE serum antibody persistence data of subjects up to 10years after the first booster with FSME-IMMUN. This report presents the results of 2 follow-up studies in the same study population of 315 healthy adults. Blood was drawn to assess the seropersistence of TBE virus antibodies yearly, from 2-5 and 7-10years after the first booster vaccination with FSME-IMMUN administered during a previous study. The timing of the second booster vaccination was dependent on the level of serum TBE antibodies observed during yearly follow-up serology observations. The current follow up showed that adult recipients were 84.9% seropositive 10years after a 3 dose primary series and the first booster vaccination of FSME-IMMUN. Seropositivity rates were even higher (88.6%) in subjects below 50years of age. ClinicalTrials.gov Identifier: NCT00503529. ClinicalTrials.gov Identifier: NCT01582698.

Antigen presentation in allergic sensitization.

IgE antibodies, when cross-linked by allergen on the surface of effector cells such as mast cells and basophils, are known to be directly responsible for immediate type hypersensitivity reactions. In addition, IgE may be involved in other, indirect, mechanisms, fundamental to the pathogenesis of allergic diseases, such as enhancement of the antigen capturing capacity of antigen presenting cells. IgE mediated antigen presentation could lead to a continuous activation of the immune system by very low concentrations of allergen. As a result, Th2 cell populations may expand and may induce more B cells to switch to IgE production. Subsequently, the overproduction of IgE and Th2 cells in a patient may explain the clinical observation that certain allergic patients deteriorate from sensitivity to a single group of allergens to sensitivity to multiple groups of allergens. Therefore, control of IgE production is not only important for the treatment of allergic symptoms, but may also regulate deterioration of allergy via the mechanism of CD23/IgE mediated allergen presentation by naive B cells. The role that monocytes, which have recently been found to express Fc epsilon RI, play in the pathogenesis of allergy, remains speculative. We hypothesize that their role may be to remove IgE from the circulation and re-direct the immune response from naive B cells. IgG antibodies which cannot be used for antigen uptake by B cells also direct the immune response to monocytes.

Different growth factor requirements for human Th2 cells may reflect in vivo induced anergy.

We previously reported the isolation of allergen-specific Th2 lines and clones from atopy patch test (APT) sites of atopic dermatitis (AD) patients. Upon stimulation with allergen or anti-CD3+ phorbol myristate acetate (PMA) IL-4 was released with or without IL-5, while no (or extremely low concentrations of) IL-2 and interferon-gamma (IFN-gamma) were detectable. A high IL-4/IFN-gamma ratio facilitates production of allergen-specific IgE, of which high levels are observed in AD patients. Here we show that the above mentioned Th2 cells are notably different from murine Th2 cells. Not IL-4, which is the autocrine acting growth factor for murine Th2 cells, but IL-2 was needed for proliferation of these human APT-derived Th2 lines and clones. Of significance, unless exogenous IL-2 was added, no proliferative response to allergen, presented by Epstein-Barr virus-transformed B (EBV-B) cells, non-T cells or IgE-bearing Langerhans cells (LC), occurred. Lack of proliferation and IL-2 production after full T cell receptor (TCR) triggering is a characteristic first described for in vitro anergized T cells. However, like the clones we describe in this study, anergic T cells may retain production of cytokines other than IL-2. A further resemblance between anergic T cells and the human Th2 clones reported here is that IL-4 can enhance IL-2-driven proliferation, but is not capable of inducing T cell growth by itself. The absence of IL-4-driven proliferation differentiates human Th2 cells from murine Th2 cells. Both produce IL-4 when stimulated in a cognate fashion, but only murine Th2 cells will proliferate. We conclude that the presently reported human Th2 cells are different from murine Th2 cells, in that they need other T cells to produce IL-2 required for their expansion. Moreover, the Th2 cells phenotypically resemble anergic T cells. As yet, however, we have no clue as to whether these features account for the current Th2 cells only or for human Th2 cells in general. We hypothesize that the Th2 phenotype of AD skin-derived, allergen-specific T cells may be induced in vivo by LC, which lack CD80, and therefore do not provide secondary signals through CD28-CD80 interaction.