After vaccination of humans with tick-borne encephalitis virus (TBEV) vaccine, the extent of cross-neutralization between viruses of the European, Far Eastern, and Siberian subtypes of TBEV and Omsk hemorrhagic fever virus (OHFV) was analyzed. Hybrid viruses that encode the TBEV surface proteins for representative viruses within all subtypes, and OHFV, were constructed using the West Nile virus (WNV) backbone as vector. These viruses allow for unbiased head-to-head comparison in neutralization assays because they exhibit the antigenic characteristics of the TBEV strains from which the surface proteins were derived and showed equivalent biologic properties in cell culture. Human serum samples derived from a TBEV vaccine trial were analyzed and revealed comparable neutralizing antibody titers against European, Far Eastern, and Siberian subtype viruses, indicating equally potent cross-protection against these TBEV strains and a somewhat reduced but still protective neutralization capacity against more distantly related viruses, such as OHFV.
A clinical study was carried out to evaluate the persistence of tick-borne encephalitis (TBE) antibodies 2 and 3 years after a primary vaccination series (three-dose regimen), and to assess the antibody response to a booster vaccination with FSME-IMMUN. Volunteers (N = 347, 18-67 years) who had received two doses of either FSME-IMMUN or Encepur adults and a third vaccination with FSME-IMMUN were enrolled. Seropositivity rates were assessed by ELISA and neutralization test (NT). After the primary series, seropositivity rates were 99.1% as determined by ELISA and 100% by NT, decreasing to 85% and 96.8% in the first two years and to 88.7% and 95.4% after 3 years. Following booster vaccination, 100% of subjects were seropositive. Age was the only variable with a significant influence on the probability of remaining TBE seropositive 2 or 3 years after the third vaccination. In subjects aged 18-50 years, the pre-booster seropositivity rate was higher (88.7% and 92.3% after 2 and 3 years, respectively) than in those aged 51-67 years (65.5% and 70.9% after 2 and 3 years, respectively). Adverse events after booster vaccination occurred with a low frequency and were predominantly mild. An annual TBE antibody decline rate of 0.58 (based on NT) was estimated to lead to antibody titer decrease from e.g., 260 to 45.6 after 3 years. To conclude, a booster vaccination with FSME-IMMUN, administered 3 years after primary vaccination, is well tolerated and induces a
Summary' IgE antibodies, when cross-linked by allergen on the surface of effector cells such as mast cells and basophils, arc 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 FCERL 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.
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