Identification of antigens presented by MHC for vaccines against tuberculosis

Mycobacterium tuberculosis (M.tb) is responsible for more deaths globally than any other pathogen. The only available vaccine, bacillus Calmette-Guérin (BCG), has variable efficacy throughout the world. A more effective vaccine is urgently needed. The immune response against tuberculosis relies, at least in part, on CD4+ T cells. Protective vaccines require the induction of antigen-specific CD4+ T cells via mycobacterial peptides presented by MHC class-II in infected macrophages. In order to identify mycobacterial antigens bound to MHC, we have immunoprecipitated MHC class-I and class-II complexes from THP-1 macrophages infected with BCG, purified MHC class-I and MHC class-II peptides and analysed them by liquid chromatography tandem mass spectrometry. We have successfully identified 94 mycobacterial peptides presented by MHC-II and 43 presented by MHC-I, from 76 and 41 antigens, respectively. These antigens were found to be highly expressed in infected macrophages. Gene ontology analysis suggests most of these antigens are associated to membranes and involved in lipid biosynthesis and transport. The sequences of selected peptides were confirmed by spectral match validation and immunogenicity evaluated by IFN-gamma ELISpot against peripheral blood mononuclear cell from volunteers vaccinated with BCG, M.tb latently infected subjects or patients with tuberculosis disease. Three antigens were expressed in viral vectors, and evaluated as vaccine candidates alone or in combination in a murine aerosol M.tb challenge model. When delivered in combination, the three candidate vaccines conferred significant protection in the lungs and spleen compared with BCG alone, demonstrating proof-of-concept for this unbiased approach to identifying new candidate antigens

Corn Yield Potential and Optimal Soil Productivity in Irrigated Corn/Soybean Systems

In 1999, an interdisciplinary research team at the University of Nebraska established a field experiment to (1) quantify and understand the yield potential of corn and soybean under irrigated conditions, (2) identify efficient crop management practices to achieve yields that approach potential levels, and (3) determine the energy use efficiency, global warming and soil C-sequestration potential of intensively managed corn systems. The experiment compares systems that represent different levels of management intensity expressed as combinations of crop rotation (continuous corn, corn-soybean), plant density (low, medium, high) and nutrient management (recommended best management vs. intensive management). Detailed measurements include soil nutrient dynamics and C balance, crop growth and development, nutrient uptake and components of yield of corn and soybean, radiation use efficiency, soil surface fluxes of greenhouse gases, root biomass, C inputs through crop residues, translocation of non-structural carbohydrates, and amount, composition and activity of the microbial biomass. Selected results for corn are presented

Corn Yield Potential and Optimal Soil Productivity in Irrigated Corn/Soybean Systems

In 1999, an interdisciplinary research team at the University of Nebraska established a field experiment to (1) quantify and understand the yield potential of corn and soybean under irrigated conditions, (2) identify efficient crop management practices to achieve yields that approach potential levels, and (3) determine the energy use efficiency, global warming and soil C-sequestration potential of intensively managed corn systems. The experiment compares systems that represent different levels of management intensity expressed as combinations of crop rotation (continuous corn, corn-soybean), plant density (low, medium, high) and nutrient management (recommended best management vs. intensive management). Detailed measurements include soil nutrient dynamics and C balance, crop growth and development, nutrient uptake and components of yield of corn and soybean, radiation use efficiency, soil surface fluxes of greenhouse gases, root biomass, C inputs through crop residues, translocation of non-structural carbohydrates, and amount, composition and activity of the microbial biomass. Selected results for corn are presented

Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff