Critical review of the safety assessment of nano-structured silica additives in food.

The development of nano-materials is viewed as one of the most important technological advances of the 21st century and new applications of nano-sized particles in the production, processing, packaging or storage of food are expected to emerge soon. This trend of growing commercialization of engineered nano-particles as part of modern diet will substantially increase oral exposure. Contrary to the proven benefits of nano-materials, however, possible adverse health effects have generally received less attention. This problem is very well illustrated by nano-structured synthetic amorphous silica (SAS), which is a common food additive since several decades although the relevant risk assessment has never been satisfactorily completed. A no observed adverse effect level of 2500 mg SAS particles/kg body weight per day was derived from the only available long-term administration study in rodents. However, extrapolation to a safe daily intake for humans is problematic due to limitations of this chronic animal study and knowledge gaps as to possible local intestinal effects of SAS particles, primarily on the gut-associated lymphoid system. This uncertainty is aggravated by digestion experiments indicating that dietary SAS particles preserve their nano-sized structure when reaching the intestinal lumen. An important aspect is whether food-borne particles like SAS alter the function of dendritic cells that, embedded in the intestinal mucosa, act as first-line sentinels of foreign materials. We conclude that nano-particles do not represent a completely new threat and that most potential risks can be assessed following procedures established for conventional chemical hazards. However, specific properties of food-borne nano-particles should be further examined and, for that purpose, in vitro tests with decision-making cells of the immune system are needed to complement existing in vivo studies.

Assessment of a cellular vaccination approach consisting of crawling dendritic cells (CDCs) transduced with HSV-1-Deltapac vectors.

Crawling dendritic cells (CDCs) and herpes simplex virus-1 (HSV-1) amplicon vectors were utilized in this study: (1) to evaluate whether CDCs can be transduced by HSV-1 amplicon vectors; (2) to assess the effects of HSV-1 infections on structure and functions of CDCs; (3) to assess the capabilities of the transduced CDC to express, process, and present the transgene products; and (4) to induce in vitro and in vivo priming of T cells and B cells. CDC supported amplicon-mediated transgene expression while retaining the ability to perform mixed lymphocyte reaction (MLR) and priming of naive T cells. Then it was tested whether transduced CDC were able to initiate immunity against either the amplicon particle and/or the product encoded by the delivered transgene by injecting groups of mice with transduced CDCs expressing GFP or LacZ. Spleen cells of these mice were stimulated by co-incubation with cells expressing: (1) either one of the transgenes (GFP or LacZ), (2) peptides of beta-gal, or (3) peptides of HSV-1 glycoprotein B (gB). Interestingly, no significant cytotoxic T lymphocyte (CTL) activity against the transgenes or against gB was observed. In contrast, mice developed high levels of antibodies against gB and LacZ.Mainly, the findings that CDCs not only express amplicon-delivered transgene, but were able to induce MLR and priming of naïve T cells against the transduced antigen, open up unexpected possibilities and the likelihood to use CDCs as a vehicle for cellular immunization against any transduced antigens. However, these results indicate that HSV-1 amplicon-transduced CDCs induce effective priming and a humoral response, but no strong cell-mediated immune response.