Measles virus as vaccine platform against highly pathogenic emerging viruses

Highly pathogenic viruses are a significant global danger since they can be spread by worldwide travel and trade almost without restriction. One particular threat comes from emerging infections, for which no adequate treatment options currently exist. To guard against local or global outbreaks of these viruses, the development of protective vaccines at an early stage is therefore a desirable form of intervention. Vector-based vaccine platforms, such as that of replication-competent recombinant measles virus (rMV), constitute good prospective vaccine candidates, since they have the potential to allow for an easy exchange of antigen-encoding genes, thereby enabling rapid vaccine production after standardisation. To assess their suitability as a potential vaccine platform against highly infectious viral pathogens, rMVs were generated as part of the practical element of this thesis. These encoded for antigens of the following emerging pathogens: Middle East respiratory syndrome coronavirus (MERS-CoV), influenza virus H7N9 or Crimean-Congo haemorrhagic fever virus (CCHFV). Insertions of antigen-encoding genes resulted in the detectable expression of the MERS-CoV spike glycoprotein in both membrane-bound (MERS-S) and soluble form (MERS-solS), the MERS-CoV nucleocapsidprotein (MERS-N), haemagluttinin or neuraminidase of H7N9 (H7 or N9), the CCHFV glycoprotein Gc (CCHFV-Gc); and the CCHFV-nucleocapsid protein (CCHFV-N), in cells infected with respective vaccines. Immunisation of MV susceptible mice with MERS-S-, MERS-solS-, H7-, or N9-encoding vaccines also resulted in the induction of humoral immune responses. These included virus-neutralising antibodies (nAbs), if mice were vaccinated with MV-MERS-S, MV-MERS-solS or MV-H7. Generation of syngeneic for the respective antigens' transgenic dendritic cell (DC) cell lines, moreover, enabled an efficient re-stimulation of antigen-specific T cells without knowledge of immunogenic epitopes or the availability of antigens as proteins. When using these transgenic DC cell lines, MV-MERS-S-, MV-MERS-solS-, MV-MERS-N-, and MV-H7-induced cellular immune responses were demonstrated in an IFN-γ-ELISpot. Moreover, MERS-S specific CD8+T cells of immunised mice responded to respective re-stimulation by MERS-S-dependent proliferation and MERS-S-specific cytotoxicity. A reduction of viral loads, as well as virus-induced inflammation of lung tissue, was observed in MV-MERS-S- or MV-MERS-solS-vaccinated mice within a MERS-CoV challenge model. This impressively demonstrated the protective efficacy of an MV-based vaccine against MERS-CoV. In the second part of this thesis, MERS-CoV-induced innate immune responses in human and murine antigen-presenting cells (APCs) were analysed. As a result, human plasmoid DCs (pDCs) were identified as a source of significant amounts of antiviral type I (IFN-α, IFN-β) and Typ III (IFN-λ) interferons (IFNs), which were secreted upon infection with MERS-CoV. As a so far exclusively-identified source of type I and III IFNs pDC might hence play a significant role in MERS-CoV-induced pathogenesis in humans. Thus, by using MERS-CoV as an example, this thesis identified several key interactions between an emerging pathogen and defined immune cells, which might prove to be of clinical significance, particularly in the future development of antiviral drugs. As potential vaccine candidate, an MV-based vaccine platform was generated as part of this thesis; and its protection efficacy was demonstrated. A rapidly conducted production of MV-based vaccine platforms against three different viral pathogens, an efficient induction of humoral and cellular immunity as well as protection efficacy in a challenge model indicated the potential of recombinant MV to be used as an effective vaccine platform to protect against emerging viral pathogens

Encouraging Pro-Environmental Behaviour: Affordances and Institutional Logics in IS-enabled Organisational Sustainability Transformations

While many studies have addressed encouraging employees’ pro-environmental behaviour (PEB) in the workplace, the roles of structures and institutions have received little attention and thus re-main unclear. We draw on the concept of affordances as being enacted and embedded in institu-tional logics, which provide a frame of reference for individual and organisational behaviours. Given our emphasis on organisational sustainability transformations, we explain how organisa-tions can encourage their employees to act pro-environmentally in the workplace with the help of green information systems (Green IS). We address technological, organisational, and human fac-tors that strengthen PEB. Thus, we respond to the call to bring together institutional logics and affordance theory. We present preliminary findings of 55 semi structured interviews with inform-ants from 20 companies, along with internal and external documents. This allows us to develop a pro-environmental corporate logic, which guides employees’ PEB in our case companies. These preliminary findings allow us to develop a research agenda on the interplay of this institutional logic and motivational affordances. We conclude with an outlook on how to tackle the emerging research questions

Novel dry electrode EEG headbands for home use: comparing performance and comfort

Monitoring brain activity at home using electroencephalography (EEG) is an increasing trend for both medical and non-medical applications. Gel-based electrodes are not suitable due to the gel application requiring extensive preparation and cleaning support for the patient or user. Dry electrodes can be applied without prior preparation by the patient or user. We investigate and compare two dry electrode headbands for EEG acquisition: a novel hybrid dual-textile headband comprising multipin and multiwave electrodes and a neoprene-based headband comprising hydrogel and spidershaped electrodes. We compare the headbands and electrodes in terms of electrode-skin impedance, comfort, electrode offset potential and EEG signal quality. We did not observe considerable differences in the power spectral density of EEG recordings. However, the hydrogel electrodes showed considerably increased impedances and offset potentials, limiting their compatibility with many EEG amplifiers. The hydrogel and spider-shaped electrodes required increased adduction, resulting in a lower wearing comfort throughout the application time compared to the novel headband comprising multipin and multiwave electrodes

Tailored parameter optimization methods for ordinary differential equation models with steady-state constraints

Background: Ordinary differential equation (ODE) models are widely used to describe (bio-)chemical and biological processes. To enhance the predictive power of these models, their unknown parameters are estimated from experimental data. These experimental data are mostly collected in perturbation experiments, in which the processes are pushed out of steady state by applying a stimulus. The information that the initial condition is a steady state of the unperturbed process provides valuable information, as it restricts the dynamics of the process and thereby the parameters. However, implementing steady-state constraints in the optimization often results in convergence problems. Results: In this manuscript, we propose two new methods for solving optimization problems with steady-state constraints. The first method exploits ideas from optimization algorithms on manifolds and introduces a retraction operator, essentially reducing the dimension of the optimization problem. The second method is based on the continuous analogue of the optimization problem. This continuous analogue is an ODE whose equilibrium points are the optima of the constrained optimization problem. This equivalence enables the use of adaptive numerical methods for solving optimization problems with steady-state constraints. Both methods are tailored to the problem structure and exploit the local geometry of the steady-state manifold and its stability properties. A parameterization of the steady-state manifold is not required. The efficiency and reliability of the proposed methods is evaluated using one toy example and two applications. The first application example uses published data while the second uses a novel dataset for Raf/MEK/ERK signaling. The proposed methods demonstrated better convergence properties than state-of-the-art methods employed in systems and computational biology. Furthermore, the average computation time per converged start is significantly lower. In addition to the theoretical results, the analysis of the dataset for Raf/MEK/ERK signaling provides novel biological insights regarding the existence of feedback regulation. Conclusion: Many optimization problems considered in systems and computational biology are subject to steady-state constraints. While most optimization methods have convergence problems if these steady-state constraints are highly nonlinear, the methods presented recover the convergence properties of optimizers which can exploit an analytical expression for the parameter-dependent steady state. This renders them an excellent alternative to methods which are currently employed in systems and computational biology

Guide on Incentives for Responsible Investment in Agriculture and Food Systems

To support implementation of the Principles for Responsible Investment in Agriculture and Food Systems (CFS RAI), CCSI has developed resources for governments and other stakeholders in partnership with the Food and Agriculture Organisation of the United Nations (FAO). This work includes an online course on creating an enabling environment for responsible investment in agriculture and food systems. The course is freely available, accessible online and available for download. Part I highlights the features and key players of an enabling environment that promotes responsible investment in agriculture and food security. Part II addresses multi-stakeholder engagement in the design of legal and institutional frameworks that govern investment. CCSI has also developed a Guide on Incentives for Responsible Investment in Agriculture and Food Systems. The Guide aims to provide policymakers with guidance on how investment incentives can be used to enhance responsible investment in agriculture and food systems--including by noting when incentives should not be used. It offers practical guidance on how to design, implement, monitor, and evaluate investment incentives that are aligned with the CFS RAI principles