Formulation considerations for the development of adjuvanted vaccines

vaccines based on highly purified protein antigens. However, there are only a few adjuvants that are used in licensed human vaccines, with aluminum salts (AlOOH and AlPO4) and squalene emulsions (AS03, MF59) being the most widely injected adjuvants in humans. While simple aluminum salts and emulsion adjuvants are very good at increasing antibody and Th-2 responses, they often lack the ability to induce strong Th-1 type cellular responses. One approach to increase the capacity of these adjuvants to induce Th-1 responses is to combine them with a small molecular weight immunopotentiator, such as a Toll-like receptor (TLR) agonist. We and others found that formulation plays an important role when developing such adjuvant combinations. With the example of a small molecule TLR-4 agonist, E6020, combined respectively to aluminum salt and to a squalene emulsion, this presentation will highlight some key formulation parameters that control the safety, potency and stability of these adjuvant combinations. References: Haensler J, Probeck P, Su J, Piras F, Dalençon F, Cotte JF, Chambon V, Iqbal SM, Hawkins L, Burdin N. Design and preclinical characterization of a novel vaccine adjuvant formulation consisting of a synthetic TLR4 agonist in a thermoreversible squalene emulsion. Int J Pharm. 2015;486(1-2):99-111. Visan L, Sanchez V, Kania M, de Montfort A, de la Maza LM, Ausar SF. Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis. Hum Vaccin Immunother. 2016;12(9):2341-50

Risk preferences under heterogeneous environmental risk

We study risk preferences and their determinants for commercial cattle farmers in Namibia who are subject to high and heterogeneous precipitation risk, using data from questionnaire and field experiments, simulated data for on-farm precipitation risk and data on famers’ previous place of residence. We find that the relationship between risk preferences and precipitation risk is contingent on early-life experience with this risk. We also find that adult farmers self-select themselves onto farms according to their risk preferences. Results are not confounded by background risks or liquidity constraint.risk preferences, environmental risk, experimental elicitation, endogenous preferences, self-selection, field experiment

Assessing the robustness of projected precipitation changes over central Africa on the basis of a multitude of global and regional climate projections

It is well accepted within the scientific community that a large ensemble of different projections is required to achieve robust climate change information for a specific region. For this purpose we have compiled a state-of-the-art multi-model multi-scenario ensemble of global and regional precipitation projections. This ensemble combines several global projections from the CMIP3 and CMIP5 databases, along with some recently downscaled regional CORDEX-Africa projections. Altogether daily precipitation data from 77 different climate change projections is analysed; separated into 31 projections for a high and 46 for a low emission scenario. We find a robust indication that, independent of the underlying emission scenario, annual total precipitation amounts over the central African region are not likely to change severely in the future. However some robust changes in precipitation characteristics, like the intensification of heavy rainfall events as well as an increase in the number of dry spells during the rainy season are projected for the future. Further analysis shows that over some regions the results of the climate change assessment clearly depend on the size of the analyzed ensemble. This indicates the need of a "large-enough" ensemble of independent climate projections to allow for a reliable climate change assessment. © 2013 The Author(s)

Non-viral approaches to gene therapy

Several advances in non-viral gene transfer technology have been reported over the past year. Cationic lipids have been successfully used to deliver genes in vivo, providing a clear alternative to recombinant viruses. In addition, investigators have demonstrated that direct application of DNA via injection or particle bombardment can be used for vaccination. Analysis of the mechanisms employed by viruses to invade cells has demonstrated a crucial role for membrane-active proteins or peptides in the entry process. Several non-viral systems that include membrane-active elements are now available

Peptide synthesis by recombinant Fasciola hepatica cathepsin L1

Synthesis of the tripeptide Z-Phe-Arg-SerNH2 has been accomplished by a recombinant cysteine protease, cathepsin L1 from liver fluke (Fasciola hepatica), using Z-Phe-Arg-OMe as acyl acceptor and SerNH2 as nucleophile in 0.1 M ammonium acetate pH 9.0–12.5% v/v acetonitrile at 37 °C. LC–MS detection indicated tripeptide formation after 10 min, continuing up to 5.5 h. The ester Z-Phe-Arg-OMe was detected throughout the experiment but the hydrolysis product Z-Phe-Arg-OH appeared early and in quite large amounts. We believe that this is the first application of a parasite protease in enzymatic peptide synthesis

Case study for the assessment of the biogeophysical effects of a potential afforestation in Europe

BACKGROUND: A regional-scale sensitivity study has been carried out to investigate the climatic effects of forest cover change in Europe. Applying REMO (regional climate model of the Max Planck Institute for Meteorology), the projected temperature and precipitation tendencies have been analysed for summer, based on the results of the A2 IPCC-SRES emission scenario simulation. For the end of the 21st century it has been studied, whether the assumed forest cover increase could reduce the effects of the greenhouse gas concentration change. RESULTS: Based on the simulation results, biogeophysical effects of the hypothetic potential afforestation may lead to cooler and moister conditions during summer in most parts of the temperate zone. The largest relative effects of forest cover increase can be expected in northern Germany, Poland and Ukraine, which is 15-20% of the climate change signal for temperature and more than 50% for precipitation. In northern Germany and France, potential afforestation may enhance the effects of emission change, resulting in more severe heavy precipitation events. The probability of dry days and warm temperature extremes would decrease. CONCLUSIONS: Large contiguous forest blocks can have distinctive biogeophysical effect on the climate on regional and local scale. In certain regions of the temperate zone, climate change signal due to greenhouse gas emission can be reduced by afforestation due to the dominant evaporative cooling effect during summer. Results of this case study with a hypothetical land cover change can contribute to the assessment of the role of forests in adapting to climate change. Thus they can build an important basis of the future forest policy

A multi-model climate response over tropical Africa at +2 °C

The impact of a +2 °C global warming on temperature and precipitation over tropical Africa is examined, based on an ensemble of 12 regional climate model scenario simulations. These 12 scenarios are re-phased so that they all correspond to the same global warming of 2 °C with respect to pre-industrial conditions. The continental temperature increase is above the global average. If heat waves are defined with the same temperature threshold in the reference climate and in the scenario, their frequency increases by a factor of 10. When the temperature threshold is adapted to future conditions, there is still a slight increase in frequency. The average precipitation does not show a significant response, due to model-to-model spread. However two compensating phenomena occur, which are robust among the models: (a) the number of rain days decreases whereas the precipitation intensity increases, and (b) the rain season occurs later during the year with less precipitation in early summer and more precipitation in late summer. Simulated daily temperature and precipitation data are combined in two impact models, one for the hydrology of the Nile and Niger basins, one for the food security of the different countries. They show that the main feature of the climate change is not a continuous trend signal, but an alternation of dry and wet decadal to multidecadal episodes