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117 results on '"Hirschberg S"'

1. An efficient and scalable method for the production of immunogenic SARS-CoV-2 virus-like particles (VLP) from a mammalian suspension cell line

Author

Hirschberg, S., Ghazaani, F., Ben Amor, G., Pydde, M., Nagel, A., Germani, S., Monica, L., Schlör, A., Bauer, H., Hornung, J., Voetz, M., Dwai, Y., Scheer, Benjamin, Ringel, F., Kamal-Eddin, O., Harms, C., Füner, J., Adrian, Lorenz, Pruß, A., Schulze-Forster, K., Hanack, K., Kamhieh-Milz, J., Hirschberg, S., Ghazaani, F., Ben Amor, G., Pydde, M., Nagel, A., Germani, S., Monica, L., Schlör, A., Bauer, H., Hornung, J., Voetz, M., Dwai, Y., Scheer, Benjamin, Ringel, F., Kamal-Eddin, O., Harms, C., Füner, J., Adrian, Lorenz, Pruß, A., Schulze-Forster, K., Hanack, K., and Kamhieh-Milz, J.

Abstract

The rapid evolution of new SARS-CoV-2 variants poses a continuing threat to human health. Vaccination has become the primary therapeutic intervention. The goal of the current work was the construction of immunogenic virus-like particles (VLPs). Here, we describe a human cell line for cost-efficient and scalable production of immunogenic SARS-CoV-2 VLPs. The modular design of the VLP-production platform facilitates rapid adaptation to new variants. Methods: The N, M-, and E-protein genes were integrated into the genome of Expi293 cells (ExpiVLP_MEN). Subsequently, this cell line was further modified for the constitutive expression of the SARS-CoV-2 spike protein. The resulting cell line (ExpiVLP_SMEN) released SARS-CoV-2 VLP upon exposure to doxycycline. ExpiVLP_SMEN cells were readily adapted for VLP production in a 5 L bioreactor. Purified VLPs were quantified by Western blot, ELISA, and nanoparticle tracking analysis and visualized by electron microscopy. Immunogenicity was tested in mice. Results: The generated VLPs contained all four structural proteins, are within the size range of authentic SARS-CoV-2 virus particles, and reacted strongly and specifically with immunoserum from naturally infected individuals. The VLPs were stable in suspension at 4 °C for at least 10 weeks. Mice immunized with VLPs developed neutralizing antibodies against lentiviruses pseudotyped with the SARS-CoV-2 spike protein. The flexibility of the VLP-production platform was demonstrated by the rapid switch of the spike protein to a new variant of concern (BA.1/Omicron). The present study describes an efficient, scalable, and adaptable production method of immunogenic SARS-CoV-2 VLPs with therapeutic potential.

Published
2023

24. Environmental inventories for future electricity supply systems for Switzerland

Author

Dones, R. and Hirschberg, S.

Subjects
Switzerland -- Energy policy, Environmental impact analysis, Petroleum, energy and mining industries
Abstract

Byline: R. Dones, S. Hirschberg The Swiss Association of Producers and Distributors of Electricity (VSE) identified a number of possible supply mix options to meet the future electricity demand in Switzerland. In this context, PSI, in co-operation with ETHZ, analysed environmental inventories for the selected electricity supply systems. Life Cycle Analysis (LCA) was used to establish the inventories, covering the complete energy chains associated with fossil, nuclear and renewable systems. The assessment was performed on three levels: (1) individually for each system considered; (2) comparison of systems; (3) comparison of supply mix options. In absolute value, the emissions of the major pollutants considered are, in most cases, significantly reduced in comparison with the currently operating systems. Due to the considerable advancements in fossil power plant technologies, the relative importance of other activities increases in the fossil energy systems. Selected results for systems and supply options are given in the present paper.

Published
2003

26. Requirement Analysis and Implementation of Multicriteria Analysis in the NEEDS Project

Author

Makowski, M., Granat, J., Ren, H., Schenler, W., and Hirschberg, S.

Abstract

This report specifies the requirements for and implementation of the multicriteria analysis of future energy technologies performed by a large number of stakeholders within the EU-funded integrated projct NEEDS. The report is composed of two main parts and the appendix. The first part starts with a summary of the objectives of the analysis followed by a detailed specifiation of the analyzed problem, in particular the analysis context, discussion of the sets of criteria and alternatives, and the participation of the stakeholders. Next, the planned problem analysis process is first outlined, and then discussed in more detail. Finally, the requirements for the multicritria analysis are specified. The second part deals with the implementation of the dedicated Web-site developed for this analysis, and later extended to support analysis of any multicriteria choice between discrete alternatives. It starts with an overview of the problem analysis process and the corresponding basic assumptions. Te architecture of the application and its features are then presented. Lessons learned from the development and use of this application conclude this part of the report. The appendix contains a review of the state-of-the-art of applying multicriteria analysis to energy problems, as well as characteristics of three applications that exploit the multicriteria analysis methods for energy problems considered relevant to the analysis reported in this paper.

Published
2009

41. Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men.

Author

Risérus U, Sprecher D, Johnson T, Olson E, Hirschberg S, Liu A, Fang Z, Hegde P, Richards D, Sarov-Blat L, Strum JC, Basu S, Cheeseman J, Fielding BA, Humphreys SM, Danoff T, Moore NR, Murgatroyd P, O'Rahilly S, and Sutton P

Abstract

OBJECTIVE: Pharmacological use of peroxisome proliferator-activated receptor (PPAR)delta agonists and transgenic overexpression of PPARdelta in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS: The PPARdelta agonist (10 mg o.d. GW501516), a comparator PPARalpha agonist (20 mug o.d. GW590735), and placebo were given in a double-blind, randomized, three-parallel group, 2-week study to six healthy moderately overweight subjects in each group. Metabolic evaluation was made before and after treatment including liver fat quantification, fasting blood samples, a 6-h meal tolerance test with stable isotope fatty acids, skeletal muscle biopsy for gene expression, and urinary isoprostanes for global oxidative stress. RESULTS: Treatment with GW501516 showed statistically significant reductions in fasting plasma triglycerides (-30%), apolipoprotein B (-26%), LDL cholesterol (-23%), and insulin (-11%), whereas HDL cholesterol was unchanged. A 20% reduction in liver fat content (P < 0.05) and 30% reduction in urinary isoprostanes (P = 0.01) were also observed. Except for a lowering of triglycerides (-30%, P < 0.05), none of these changes were observed in response to GW590735. The relative proportion of exhaled CO(2) directly originating from the fat content of the meal was increased (P < 0.05) in response to GW501516, and skeletal muscle expression of carnitine palmitoyl-transferase 1b (CPT1b) was also significantly increased. CONCLUSIONS: The PPARdelta agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle. [ABSTRACT FROM AUTHOR]

Published
2008
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42. CD4<SUP>+</SUP> T cells induced by virus-like particles expressing a major T cell epitope down-regulate IL-5 production in an ongoing immune response to Der p 1 independently of IFN-γ production

Author

Layton, G.T., Harris, S.J., Savage, N., Lamb, J.R., Hirschberg, S., and Dallman, M.J.

Abstract

It has been previously demonstrated that hybrid Ty virus-like particles (VLP) prime effective CD8+ and CD4+ T cell responses. In this study, we investigated the effect of treating mice with Ty VLP carrying the immunodominant epitope of Der p 1 after sensitizing them to the group 1 allergen of the house dust mite Dermatophagoides pteronyssinus (Der p 1), under conditions that induce Th2 immunity. We show that i.p. treatment with the hybrid VLP abrogated allergen-specific IL-5 production and reduced allergen-specific cell proliferation. This suppression of the response was mediated by CD4+ T cells and was not accompanied by an increase in IFN-γ production.

Published
1999

43. CD4(+) T cells induced by virus-like particles expressing a major T cell epitope down-regulate IL-5 production in an ongoing immune response to Der p 1 independently of IFN-gamma production.

Author

Hirschberg, S, Layton, G T, Harris, S J, Savage, N, Dallman, M J, and Lamb, J R

Abstract

It has been previously demonstrated that hybrid Ty virus-like particles (VLP) prime effective CD8(+) and CD4(+) T cell responses. In this study, we investigated the effect of treating mice with Ty VLP carrying the immunodominant epitope of Der p 1 after sensitizing them to the group 1 allergen of the house dust mite Dermatophagoides pteronyssinus (Der p 1), under conditions that induce T(h)2 immunity. We show that i.p. treatment with the hybrid VLP abrogated allergen-specific IL-5 production and reduced allergen-specific cell proliferation. This suppression of the response was mediated by CD4(+) T cells and was not accompanied by an increase in IFN-gamma production.

Published
1999
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