A Nonintegrative Lentiviral Vector-Based Vaccine Provides Long-Term Sterile Protection against Malaria

Trials testing the RTS,S candidate malaria vaccine and radiation-attenuated sporozoites (RAS) have shown that protective immunity against malaria can be induced and that an effective vaccine is not out of reach. However, longer-term protection and higher protection rates are required to eradicate malaria from the endemic regions. It implies that there is still a need to explore new vaccine strategies. Lentiviral vectors are very potent at inducing strong immunological memory. However their integrative status challenges their safety profile. Eliminating the integration step obviates the risk of insertional oncogenesis. Providing they confer sterile immunity, nonintegrative lentiviral vectors (NILV) hold promise as mass pediatric vaccine by meeting high safety standards. In this study, we have assessed the protective efficacy of NILV against malaria in a robust pre-clinical model. Mice were immunized with NILV encoding Plasmodium yoelii Circumsporozoite Protein (Py CSP) and challenged with sporozoites one month later. In two independent protective efficacy studies, 50% (37.5–62.5) of the animals were fully protected (p = 0.0072 and p = 0.0008 respectively when compared to naive mice). The remaining mice with detectable parasitized red blood cells exhibited a prolonged patency and reduced parasitemia. Moreover, protection was long-lasting with 42.8% sterile protection six months after the last immunization (p = 0.0042). Post-challenge CD8+ T cells to CSP, in contrast to anti-CSP antibodies, were associated with protection (r = −0.6615 and p = 0.0004 between the frequency of IFN-g secreting specific T cells in spleen and parasitemia). However, while NILV and RAS immunizations elicited comparable immunity to CSP, only RAS conferred 100% of sterile protection. Given that a better protection can be anticipated from a multi-antigen vaccine and an optimized vector design, NILV appear as a promising malaria vaccine.     

Through the Eyes of Children: Perceptions of Environmental Change in Tropical Forests

This study seeks to understand children''s perceptions of their present and future environments in the highly biodiverse and rapidly changing landscapes of Kalimantan, Indonesian Borneo. We analyzed drawings by children (target age 10–15 years) from 22 villages, which show how children perceive the present conditions of forests and wildlife surrounding their villages and how they expect conditions to change over the next 15 years. Analyses of picture elements and their relationships to current landscape variables indicate that children have a sophisticated understanding of their environment and how different environmental factors interact, either positively or negatively. Children appear to have landscape-dependent environmental perceptions, showing awareness of past environmental conditions and many aspects of recent trends, and translating these into predictions for future environmental conditions. The further removed their present landscape is from the originally forested one, the more environmental change they expect in the future, particularly declines in forest cover, rivers, animal diversity and increases in temperature and natural disasters. This suggests that loss of past perceptions and associated “shifting environmental baselines” do not feature strongly among children on Borneo, at least not for the perceptions we investigated here. Our findings that children have negative expectations of their future environmental conditions have important political implications. More than other generations, children have a stake in ensuring that future environmental conditions support their long-term well-being. Understanding what drives environmental views among children, and how they consider trade-offs between economic development and social and environmental change, should inform optimal policies on land use. Our study illuminates part of the complex interplay between perceptions of land cover and land use change. Capturing the views of children through artistic expressions provides a potentially powerful tool to influence public and political opinions, as well as a valuable approach for developing localized education and nature conservation programs.     

Application of a Doehlert experimental design to the optimization of microbial degradation of crude oil in sea water by continuous culture

Summary Crude oil was degraded by a mixed bacterial community grown in continuous culture on sea water. The fermentation process included an emulsification step prior to the introduction of the substrate in the reactor, with external cell recycling by a tangential-flow filtration system. Optimization of the fermentation technique was achieved by using the surface response methodology (Doehlert experimental design). Besides reducing the number of experiments, this approach allowed optimal experimental conditions to be chosen, for the particular goal: percent degradation of crude oil (80%), biomass (7.6 g·l^-1) and degradation rate (0.73 g·l^-1·h^-1). This biodegradation process could be used as a tool to fight against pollutions by petroleum products.     

The Design and Synthesis of Bis-[4′-Azido-2,2′:6′,2″-Terpyridine Platinum(II)] Complexes with Rigid and Extended Linkers for Studying the Topology of DNA by Photoaffinity Labeling

A family of bis-[4′-Azido-2,2′:6′,2″-terpyridine platinum(II)] complexes with linear linkers of varying length have been synthesized. They have been designed to bis-intercalate into two DNA duplexes in close proximity, the azido groups allowing the sites of intercalation to be photoaffinity labeled. The linker to Pt(II) bonds are susceptible to cleavage by thiols and cyanide ion, which is a requirement for the intended method of analysis by 2D gel electrophoresis.     

Two-faced Fcab prevents polymerization with VEGF and reveals thermodynamics and the 2.15 Å crystal structure of the complex

Fcabs (Fc domain with antigen-binding sites) are promising novel therapeutics. By engineering of the C-terminal loops of the CH3 domains, 2 antigen binding sites can be inserted in close proximity. To elucidate the binding mode(s) between homodimeric Fcabs and small homodimeric antigens, the interaction between the Fcabs 448 and CT6 (having the AB, CD and EF loops and the C-termini engineered) with homodimeric VEGF was investigated. The crystal structures of these Fcabs, which form polymers with the antigen VEGF in solution, were determined. However, construction of heterodimeric Fcabs (JanusFcabs: one chain Fc-wt, one chain VEGF-binding) results in formation of distinct JanusFcab–VEGF complexes (2:1), which allowed elucidation of the crystal structure of the JanusCT6–VEGF complex at 2.15 Å resolution. VEGF binding to Janus448 and JanusCT6 is shown to be entropically unfavorable, but enthalpically favorable. Structure-function relationships are discussed with respect to Fcab design and engineering strategies.