An intact signal peptide on dengue virus E protein enhances immunogenicity for CD8+ T cells and antibody when expressed from modified vaccinia Ankara

Dengue is a global public health concern and this is aggravated by a lack of vaccines or antiviral therapies. Despite the well-known role of CD8(+) T cells in the immunopathogenesis of Dengue virus (DENV), only recent studies have highlighted the importance of this arm of the immune response in protection against the disease. Thus, the majority of DENV vaccine candidates are designed to achieve protective titers of neutralizing antibodies, with less regard for cellular responses. Here, we used a mouse model to investigate CD8(+) T cell and humoral responses to a set of potential DENV vaccines based on recombinant modified vaccinia virus Ankara (rMVA). To enable this study, we identified two CD8(+) T cell epitopes in the DENV-3 E protein in C57BL/6 mice. Using these we found that all the rMVA vaccines elicited DENV-specific CD8(+) T cells that were cytotoxic in vivo and polyfunctional in vitro. Moreover, vaccines expressing the E protein with an intact signal peptide sequence elicited more DENV-specific CD8(+) T cells than those expressing E proteins in the cytoplasm. Significantly, it was these same ER-targeted E protein vaccines that elicited antibody responses. Our results support the further development of rMVA vaccines expressing DENV E proteins and add to the tools available for dengue vaccine development.Parts of this work were supported by the InstitutoNacional de Ciência e Tecnologia de Vacinas–INCTV (National Insti-tute of Science and Technology of Vaccines) and by a FAPEMIGPPM grant (CBB, PPM-00461-11). BRQ was a CAPES/PDSE fellow-ship recipient (8815-11-9). FGF is a CNPq fellowship recipient. DCTis an ARC Future Fellow (FT110100310)

Application of a prioritisation scheme for seismic intervention in schools buildings in Italy

A risk management framework has recently been developed to assign priorities for the rehabilitation of school buildings in Italy, and to give timescales within which retrofit or demolition must take place. Since it is not practical to carry out a detailed assessment of the 60,000 Italian state and public schools, the framework is a multiple-level procedure which aims to identify the highest-risk buildings based on filters of increasing detail, and reduces the size of the building inventory at each step. The first risk ranking is based on a strength deficit, which measures the difference between the current design forces defined for the building site and an estimation of the level of seismic resistance which was required at the time of design. The second ranking is based on lateral strength calculations that are already available for a large portion of the Italian masonry building stock, and that are obtained from a survey form that is familiar to Italian engineers. Finally, a simplified displacement-based methodology is used to give a more accurate assessment of seismic risk based on a limited amount of geometrical and material data. The final assessment leads to a capacity ratio and a risk rating, which are used within a transparent procedure to assign priorities for seismic intervention, and timescales within which detailed assessment leading to retrofit or demolition must take place. The first step of the methodology has been applied herein to the school building stock within two Regions in Italy and preliminary results are presented

Plane sudden expansion flows of viscoelastic liquids

We report a systematic numerical investigation of the creeping flow of three different viscoelastic models, the UCM, Oldroyd-B and the linear form of the PTT model, through a 1:3 planar sudden expansion. Although the effect of elasticity is to reduce both the length and intensity of the recirculation region downstream of the expansion, we show that this reduction is much lower than previous studies have suggested and that, at high Deborah number, a significant region of recirculation still exists for all of the models studied