Latest advancements in process intensification to support global demand for affordable vaccines

Vaccines have a profound impact on global health, preventing illness, death, and improving the quality of life across the globe. However, the current costs of vaccine manufacturing and distribution often prevent the poorest segments of the world’s population from accessing these critical medicines. Vaccine manufacturing for global distribution typically requires large and expensive manufacturing facilities that result in high vaccine Cost of Goods and impede developing countries from initiating or expanding in-country manufacturing capabilities. One of the strategies to address this is to intensify vaccine production processes. This presentation will give an overview of a project funded by the Bill & Melinda Gates foundation that focusses on applying the latest process intensification technologies to develop a platform that dramatically increases process efficiency, decreases production scale and reduces vaccine COGs to a price of $0.15 per dose or less. This vaccine manufacturing platform combines Vero cell lines optimized for virus propagation and media capable of supporting high cell density cell growth, high cell density single-use bioreactors and high efficiency and single step purification technologies. Together, these technologies enable vaccine yields to be significantly increased, which in turn allows commercial manufacturing in a small-footprint, low cost “micro-facility” capable of delivering \u3e40M doses of vaccine per year for a CAPEX of not more than$10M and low operational costs. Such “micro-facilities” can be rapidly and inexpensively commissioned, drastically reducing vaccine COGs, facilitating rapid response and resulting in commercial manufacturing at lab scale. The platform is currently being established using Sabin IPV as the target vaccine. Current status is that Vero cell lines expressing 2-4 fold higher cell specific virus titers have been selected. These have been successfully cultured in high cell density, single-use bioreactors up to 40 million cells per mL. Following infection with Sabin poliovirus vaccine strains, a single chromatographic step using a novel membrane has resulted in 90% recoveries at 95% purity. For IPV, these yield intensifications mean that the entire commercial scale process can be operated in isolators in a footprint of ±30 m2. Combination of four of these manufacturing units in a single “micro-facility” would be capable of delivering \u3e40 million doses of trivalent sIPV per year. Performance of the manufacturing process in isolators also allows the manufacture of viral vaccines that currently require high biological safety containment in an inexpensive facility design. This presentation will discuss the technologies used in the vaccine manufacturing platform and data obtained to date on Sabin IPV in more detail

Regulatory Aspects of Mining Waste Management in the Russian Federation

The legislation defines the rights and responsibilities of subsoil users and other members of the waste management process, therefore, the state of affairs in this sphere largely depends on its quality. Modern "conflict" of legal acts, which is caused by the absence of state integrated concept of waste management, forms a chain of consequences that lead to their accumulation in the environment. The main problem is still the lack of coordination of environmental and mining legislation, misleading the subsoil users. The possibility to generate incentives for waste reduction, recycling and utilization depends on the state of the institutional environment, which determines the scope of the interaction of economic entities on the basis of the system of legal acts. The aim of the present research is to study the Russian legislation concerning the control of economic relations in the sphere of mining waste handling. In the article the definition of "waste" as the object of management and concepts underlying the regulatory framework of waste management. On the basis of statistical dynamic analysis the relations between the state of the regulatory framework in the waste management and the factors conditioning the negative trends have been identified and summarized. "Conservative" and "liberal" views on elimination of contradictions in the regulatory framework of mining waste handling have been studied. The directions of improvement of the regulatory framework in the sphere of mining waste management upon the "conservative" and "liberal" scenarios have been suggested

Assocate professor in Health Services Management, School of Management and Medical Informatics

Nursing competencies in the field of medical education is of particular significance and has always been under consideration by researchers of nursing education. In Medical Sciences the word capability or competency has been used as a broad concept, and basically refers to the knowledge, attitude, expertise and experience necessary for the effective implementation of a role and profession. Therefore, measuring these characteristics makes it possible to determine the ability or competency of nursing graduates. The present study aims to compare the competencies of graduates of bachelor of nursing of private and public universities of the province of Maragheh, which will be done on the bachelor of nursing graduates of the private "Azad" university and state university of Maragheh province. This study was performed as a survey from graduates of nursing undergraduate program of private and public universities in the province of Maragheh. Data collection tools were standard checklists of nursing profession of the Ministry of Health and Medical Education. The collected data were analyzed using software SPSS version 21 and the results of the evaluation of the graduates of two universities were compared with each other. At all stages, significant level of p<0.05 was assumed. The study found that the participants' level of knowledge and attitudes in both groups from private and public universities was low, but the status of attitudes among public university graduates with a significant (p = 0.005) difference was lower compared to Azad university graduates

Pre-hybridisation: an efficient way of suppressing endogenous biotin-binding activity inherent to biotin–streptavidin detection system

Endogenous biotin or biotinylated protein binding activity is a major drawback to biotin-avidin/streptavidin detection system. The avidin/streptavidin conjugate used to detect the complex of the biotinylated secondary antibody and the primary antibody binds to endogenous biotin or biotinylated proteins leading to non-specific signals. In Western blot, the endogenous biotin or biotinylated protein binding activity is usually manifested in the form of ~72kDa, ~75kDa and ~150kDa protein bands, which often mask the signals of interest. To overcome this problem, a method based on prior hybridisation of the biotinylated secondary antibody and the streptavidin conjugate was developed. The method was tested alongside the conventional biotin-streptavidin method on proteins extracted from zebrafish (Danio rerio) embryos. Results showed that the newly developed method efficiently suppresses the endogenous biotin or biotinylated protein binding activity inherent to the biotin-streptavidin detection system

Multidrug resistant, extended spectrum β-lactamase (ESBL)-producing Escherichia coli isolated from a dairy farm

Escherichia coli strains were isolated from a single dairy farm as a sentinel organism for the persistence of antibiotic resistance genes in the farm environment. Selective microbiological media were used to isolate 126 E. coli isolates from slurry and faeces samples from different farm areas. Antibiotic resistance profiling for 17 antibiotics (seven antibiotic classes), showed 57.9% of the isolates were resistant to between 3 and 15 antibiotics. The highest frequency of resistance was to ampicillin (56.3%), and the lowest to imipenem (1.6%), which appeared to be an unstable phenotype and was subsequently lost. Extended spectrum beta-lactamase resistance (ESBL) was detected in 53 isolates and blaCTX-M, blaTEM and blaOXA genes were detected by PCR in twelve, four and two strains, respectively. Phenotypically most isolates showing resistance to cephalosporins were AmpC rather than ESBL, a number of isolates having both activities. Phenotypic resistance patterns suggested co-acquisition of some resistance genes within subsets of the isolates. Genotyping using ERIC PCR demonstrated these were not clonal, and therefore co-resistance may be associated with mobile genetic elements. These data show a snapshot of diverse resistance genes present in the E. coli population reservoir, including resistance to historically used antibiotics as well as cephalosporins in contemporary use

The composition and oxidative stability of vegetarian omega-3 algal oil nanoemulsions suitable for functional food enrichment

Background: Long chain omega-3 polyunsaturated fatty acid (LCn3PUFA) nanoemulsion enriched foods offer potential to address habitually low oily fish intakes. Nanoemulsions increase LCn3PUFA bioavailability, but may cause lipid oxidation. This study examined oxidative stability of LCn3PUFA algal oil-in-water nanoemulsions created by ultrasound using natural and synthetic emulsifiers during 5-weeks of storage at 4, 20 and 40°C. Fatty acid composition, droplet size ranges and volatile compounds were analysed. Results: No significant differences were found for fatty acid composition at various temperatures and storage times. Lecithin nanoemulsions had significantly larger droplet size ranges at baseline and during storage regardless of temperatures. While combined Tween 40 and lecithin nanoemulsions had low initial droplet size ranges, there were significant increases at 40°C after 5-weeks storage. Gas chromatograms identified hexanal and propanal as predominant volatile compounds, along with 2-ethylfuran; propan-3-ol; valeraldehyde. The Tween 40 only nanoemulsion sample showed formation of lower concentrations of volatiles compared to lecithin samples. Formation of hexanal and propanal remained stable at lower temperatures although higher concentrations were found in nanoemulsions than bulk oil. The lecithin only sample had formation of higher concentrations of volatiles at increased temperatures despite having significantly larger droplet size ranges than the other samples. Conclusions: Propanal and hexanal were the most prevalent of five volatile compounds detected in bulk oil and lecithin and/or Tween 40 nanoemulsions. Oxidation compounds remained more stable at lower temperatures indicating suitability for enrichment of refrigerated foods. Further research to evaluate the oxidation stability of these systems within food matrices is warranted

In vivo laboratory practicals in research-led teaching: An example using glucose tolerance tests in lean and obese mice

The use of animal models is an essential part of medical research and drug development. The essential skills required to be able to do such research includes experimental design, statistical analysis and the actual handling and treating of the animals (in vivo skills). The number of students in the U.K. receiving training in handling and experimenting on animals has declined rapidly in the last few decades which has led to initiatives to increase numbers of students with these skills to meet demand. Within the Department of Pharmacology and Therapeutics at King's College London, we run a course for 2nd year undergraduates entitled “Animal models of disease and injury”. This course not only covers the theoretical and ethical aspects of using animals in research, but also contains practical laboratory classes in which students get hands-on experience using animals. One of the laboratory classes we run is a glucose tolerance test in obese and lean mice. This is an example of research-led teaching which aims to develop research skills through engaging students in research like activities. In this paper, we outline the methodology of the glucose tolerance practical and highlight some of the skills we and the students think they gain by research-led teaching such as this

Who needs what from a national health research system: Lessons from reforms to the English Department of Health's R&D system

This article has been made available through the Brunel Open Access Publishing Fund.Health research systems consist of diverse groups who have some role in health research, but the boundaries around such a system are not clear-cut. To explore what various stakeholders need we reviewed the literature including that on the history of English health R&D reforms, and we also applied some relevant conceptual frameworks. We first describe the needs and capabilities of the main groups of stakeholders in health research systems, and explain key features of policymaking systems within which these stakeholders operate in the UK. The five groups are policymakers (and health care managers), health professionals, patients and the general public, industry, and researchers. As individuals and as organisations they have a range of needs from the health research system, but should also develop specific capabilities in order to contribute effectively to the system and benefit from it. Second, we discuss key phases of reform in the development of the English health research system over four decades - especially that of the English Department of Health's R&D system - and identify how far legitimate demands of key stakeholder interests were addressed. Third, in drawing lessons we highlight points emerging from contemporary reports, but also attempt to identify issues through application of relevant conceptual frameworks. The main lessons are: the importance of comprehensively addressing the diverse needs of various interacting institutions and stakeholders; the desirability of developing facilitating mechanisms at interfaces between the health research system and its various stakeholders; and the importance of additional money in being able to expand the scope of the health research system whilst maintaining support for basic science. We conclude that the latest health R&D strategy in England builds on recent progress and tackles acknowledged weaknesses. The strategy goes a considerable way to identifying and more effectively meeting the needs of key groups such as medical academics, patients and industry, and has been remarkably successful in increasing the funding for health research. There are still areas that might benefit from further recognition and resourcing, but the lessons identified, and progress made by the reforms are relevant for the design and coordination of national health research systems beyond England.This article is available through the Brunel Open Access Publishing Fund

Hepatitis C virus infection protein network

A proteome-wide mapping of interactions between hepatitis C virus (HCV) and human proteins was performed to provide a comprehensive view of the cellular infection. A total of 314 protein–protein interactions between HCV and human proteins was identified by yeast two-hybrid and 170 by literature mining. Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HCV are enriched in highly central and interconnected proteins. A global analysis on the basis of functional annotation highlighted the enrichment of cellular pathways targeted by HCV. A network of proteins associated with frequent clinical disorders of chronically infected patients was constructed by connecting the insulin, Jak/STAT and TGFβ pathways with cellular proteins targeted by HCV. CORE protein appeared as a major perturbator of this network. Focal adhesion was identified as a new function affected by HCV, mainly by NS3 and NS5A proteins