scholarly journals Pandemic-response adenoviral vector and RNA vaccine manufacturing

2021 ◽  
Author(s):  
Zoltan Kis ◽  
Kyungjae Tak ◽  
Dauda Ibrahim ◽  
Maria M Papathanasiou ◽  
Benoit Chachuat ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Economic Feasibility ◽  
Vaccine Production ◽  
Resource Requirement ◽  
Cost Performance ◽  
Feasibility Assessment ◽  
Future Technology ◽  
Production Platform ◽  
Pandemic Response ◽  
The Impact

Rapid global COVID-19 pandemic response by mass vaccination is currently limited by the rate of vaccine manufacturing. This study presents a techno-economic feasibility assessment and comparison of three vaccine production platform technologies deployed during the COVID-19 pandemic: (1) adenovirus-vectored (AVV) vaccines, (2) messenger RNA (mRNA) vaccines, and (3) the newer self-amplifying RNA (saRNA) vaccines. Besides assessing the baseline performance of the production process, the impact of key design and operational uncertainties on the productivity and cost performance of these vaccine platforms were also evaluated using variance-based global sensitivity analysis. Cost and resource requirement projections were also computed for manufacturing multi-billion vaccine doses for covering the current global demand shortage and for providing annual booster immunizations. This model-based assessment provides key insights to policymakers and vaccine manufacturers for risk analysis, asset utilisation, directions for future technology improvements and future epidemic/pandemic preparedness, given the disease-agnostic nature of these vaccine production platforms.

scholarly journals Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand

Vaccines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 3
Author(s):  
Zoltán Kis ◽  
Cleo Kontoravdi ◽  
Robin Shattock ◽  
Nilay Shah
Keyword(s):  
Production Process ◽  
Messenger Rna ◽  
Vaccination Campaign ◽  
Vaccine Dose ◽  
Economic Feasibility ◽  
Small Scale ◽  
Production Scale ◽  
Working Volume ◽  
Global Demand ◽  
The Impact

To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA vaccines for the demand associated with a global vaccination campaign. Production process performance is assessed for three messenger RNA (mRNA) and one self-amplifying RNA (saRNA) vaccines, all currently under clinical development, as well as for a hypothetical next-generation saRNA vaccine. The impact of key process design and operation uncertainties on the performance of the production process was assessed. The RNA vaccine drug substance (DS) production rates, volumes and costs are mostly impacted by the RNA amount per vaccine dose and to a lesser extent by the scale and titre in the production process. The resources, production scale and speed required to meet global demand vary substantially in function of the RNA amount per dose. For lower dose saRNA vaccines, global demand can be met using a production process at a scale of below 10 L bioreactor working volume. Consequently, these small-scale processes require a low amount of resources to set up and operate. RNA DS production can be faster than fill-to-finish into multidose vials; hence the latter may constitute a bottleneck.

scholarly journals Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Damien van de Berg ◽  
Zoltán Kis ◽  
Carl Fredrik Behmer ◽  
Karnyart Samnuan ◽  
Anna K. Blakney ◽  
...  
Keyword(s):  
Qualitative Methodology ◽  
Quality By Design ◽  
Design Space ◽  
Emerging Infectious Diseases ◽  
Rapid Response ◽  
Vaccine Production ◽  
Production Platform ◽  
The Cost ◽  
The Impact ◽  
Rna Vaccine

AbstractRapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead of outbreaks. We are the first to apply the Quality by Design (QbD) framework to enhance rapid-response RNA vaccine manufacturing against known and future viral pathogens. This QbD framework aims to support the development and consistent production of safe and efficacious RNA vaccines, integrating a novel qualitative methodology and a quantitative bioprocess model. The qualitative methodology identifies and assesses the direction, magnitude and shape of the impact of critical process parameters (CPPs) on critical quality attributes (CQAs). The mechanistic bioprocess model quantifies and maps the effect of four CPPs on the CQA of effective yield of RNA drug substance. Consequently, the first design space of an RNA vaccine synthesis bioreactor is obtained. The cost-yield optimization together with the probabilistic design space contribute towards automation of rapid-response, high-quality RNA vaccine production.

scholarly journals Modeling Energy Communities with Collective Photovoltaic Self-Consumption: Synergies between a Small City and a Winery in Portugal

Energies ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 323
Author(s):  
Guilherme Pontes Luz ◽  
Rodrigo Amaro e Silva
Keyword(s):  
Economic Feasibility ◽  
Small City ◽  
Total System ◽  
Trade Offs ◽  
Southern Portugal ◽  
Energy Community ◽  
Individual Self ◽  
The Impact ◽  
The City ◽  
Modest Reduction

The recently approved regulation on Energy Communities in Europe is paving the way for new collective forms of energy consumption and production, mainly based on photovoltaics. However, energy modeling approaches that can adequately evaluate the impact of these new regulations on energy community configurations are still lacking, particularly with regards to the grid tariffs imposed on collective systems. Thus, the present work models three different energy community configurations sustained on collective photovoltaics self-consumption for a small city in southern Portugal. This energy community, which integrates the city consumers and a local winery, was modeled using the Python-based Calliope framework. Using real electricity demand data from power transformers and an actual winery, the techno-economic feasibility of each configuration was assessed. Results show that all collective arrangements can promote a higher penetration of photovoltaic capacity (up to 23%) and a modest reduction in the overall cost of electricity (up to 8%). However, there are clear trade-offs between the different pathways: more centralized configurations have 53% lower installation costs but are more sensitive to grid use costs (which can represent up to 74% of the total system costs). Moreover, key actor’s individual self-consumption rate may decrease by 10% in order to benefit the energy community as a whole.

scholarly journals Neurodegenerative diseases: a hotbed for splicing defects and the potential therapies

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Dunhui Li ◽  
Craig Stewart McIntosh ◽  
Frank Louis Mastaglia ◽  
Steve Donald Wilton ◽  
May Thandar Aung-Htut
Keyword(s):  
Alternative Splicing ◽  
Neurodegenerative Diseases ◽  
Messenger Rna ◽  
Muscular Atrophy ◽  
Single Gene ◽  
Synaptic Function ◽  
Coding Regions ◽  
Splicing Defects ◽  
The Impact ◽  
Splicing Patterns

AbstractPrecursor messenger RNA (pre-mRNA) splicing is a fundamental step in eukaryotic gene expression that systematically removes non-coding regions (introns) and ligates coding regions (exons) into a continuous message (mature mRNA). This process is highly regulated and can be highly flexible through a process known as alternative splicing, which allows for several transcripts to arise from a single gene, thereby greatly increasing genetic plasticity and the diversity of proteome. Alternative splicing is particularly prevalent in neuronal cells, where the splicing patterns are continuously changing to maintain cellular homeostasis and promote neurogenesis, migration and synaptic function. The continuous changes in splicing patterns and a high demand on many cis- and trans-splicing factors contribute to the susceptibility of neuronal tissues to splicing defects. The resultant neurodegenerative diseases are a large group of disorders defined by a gradual loss of neurons and a progressive impairment in neuronal function. Several of the most common neurodegenerative diseases involve some form of splicing defect(s), such as Alzheimer’s disease, Parkinson’s disease and spinal muscular atrophy. Our growing understanding of RNA splicing has led to the explosion of research in the field of splice-switching antisense oligonucleotide therapeutics. Here we review our current understanding of the effects alternative splicing has on neuronal differentiation, neuronal migration, synaptic maturation and regulation, as well as the impact on neurodegenerative diseases. We will also review the current landscape of splice-switching antisense oligonucleotides as a therapeutic strategy for a number of common neurodegenerative disorders.

scholarly journals Artificial intelligence and the future of psychiatry: Qualitative findings from a global physician survey

2020 ◽  
Vol 6 ◽  
pp. 205520762096835
Author(s):  
C Blease ◽  
C Locher ◽  
M Leon-Carlyle ◽  
M Doraiswamy
Keyword(s):  
Artificial Intelligence ◽  
Machine Learning ◽  
Medical Profession ◽  
Descriptive Analysis ◽  
Psychiatric Practice ◽  
Limited Attention ◽  
Written Responses ◽  
Future Technology ◽  
Qualitative Descriptive ◽  
The Impact

Background The potential for machine learning to disrupt the medical profession is the subject of ongoing debate within biomedical informatics. Objective This study aimed to explore psychiatrists’ opinions about the potential impact innovations in artificial intelligence and machine learning on psychiatric practice Methods In Spring 2019, we conducted a web-based survey of 791 psychiatrists from 22 countries worldwide. The survey measured opinions about the likelihood future technology would fully replace physicians in performing ten key psychiatric tasks. This study involved qualitative descriptive analysis of written responses (“comments”) to three open-ended questions in the survey. Results Comments were classified into four major categories in relation to the impact of future technology on: (1) patient-psychiatrist interactions; (2) the quality of patient medical care; (3) the profession of psychiatry; and (4) health systems. Overwhelmingly, psychiatrists were skeptical that technology could replace human empathy. Many predicted that ‘man and machine’ would increasingly collaborate in undertaking clinical decisions, with mixed opinions about the benefits and harms of such an arrangement. Participants were optimistic that technology might improve efficiencies and access to care, and reduce costs. Ethical and regulatory considerations received limited attention. Conclusions This study presents timely information on psychiatrists’ views about the scope of artificial intelligence and machine learning on psychiatric practice. Psychiatrists expressed divergent views about the value and impact of future technology with worrying omissions about practice guidelines, and ethical and regulatory issues.

Transit networks, social contacts and open data meet public transportation plans for post-COVID-19: A Canadian case study

2021 ◽  
Author(s):  
Oliver Benning ◽  
Jonathan Calles ◽  
Burak Kantarci ◽  
Shahzad Khan
Keyword(s):  
Public Transportation ◽  
Population Distribution ◽  
Open Data ◽  
Practical Method ◽  
Municipal Services ◽  
Transit Network ◽  
Research Findings ◽  
Pandemic Response ◽  
The Impact

This article presents a practical method for the assessment of the risk profiles of communities by tracking / acquiring, fusing and analyzing data from public transportation, district population distribution, passenger interactions and cross-locality travel data. The proposed framework fuses these data sources into a realistic simulation of a transit network for a given time span. By shedding credible insights into the impact of public transit on pandemic spread, the research findings will help to set the groundwork for tools that could provide pandemic response teams and municipalities with a robust framework for the evaluations of city districts most at risk, and how to adjust municipal services accordingly.

scholarly journals The Impact of Dietary Compounds in Functional Foods on MicroRNAs Expression

2021 ◽  
Author(s):  
Wittaya Chaiwangyen
Keyword(s):  
Messenger Rna ◽  
Positive Impact ◽  
Biologically Active ◽  
Transcriptional Gene Silencing ◽  
Cellular Mirnas ◽  
Rna Molecules ◽  
Post Transcriptional Gene Silencing ◽  
Molecular Machinery ◽  
Different Origins ◽  
The Impact

MicroRNAs (miRNAs) are a class of non-coding endogenous RNA molecules that are involved in post-transcriptional gene silencing via binding to their target messenger RNA, leading to mRNA degradation or translational repression. MicroRNAs can be modulated by several factors including hormones, transcription factors, and dietary compounds. These biologically active compounds have positive impact on the progression of human pathology including non-communicable diseases, which indicating that administration of diet may have potential as therapeutic agents in modulating the risk of chronic diseases. Interestingly, evidence emerging in recent years suggests that dietary miRNAs can be absorbed in human circulation, modulated human gene expression and biological functions. The exploitation of the miRNA functioning within different origins, cellular miRNAs and dietary miRNAs will help us to understand the molecular machinery as well as the regulatory mechanisms involved in fundamentally important biological processes. Therefore, this knowledge may be applied of natural bioactive compounds in preventive or therapeutic approaches.

scholarly journals Resuming In-Person Classes under COVID-19: Evaluating Assigned Seating Protocols in Limiting Contacts at Postsecondary Institutions

2021 ◽  
Author(s):  
Daniel Daly-Grafstein ◽  
Patricia Daly ◽  
Reka Gustafson
Keyword(s):  
Returning Students ◽  
Postsecondary Institutions ◽  
Contact Tracing ◽  
Severe Illness ◽  
Post Secondary ◽  
Pandemic Response ◽  
Enrollment Data ◽  
The Impact ◽  
Academic Year ◽  
Reducing Potential

In order to limit the spread of COVID-19, Canadian postsecondary institutions are offering the majority of classes online for the 2020-21 academic year. The goal of Canada's public health pandemic response is to reduce severe illness and mortality from COVID-19 while minimizing social disruption. To achieve this goal, post secondary institutions need practical tools to limit COVID-19 spread and facilitate contact tracing while returning students to in-person instruction. In this paper, we explore the impact of assigned seating for students attending in-person classes in reducing potential contacts. We conduct a variety of seating simulations using student enrollment data and measure the number of potential contacts under each scenario. We find that assigning seats to students significantly reduces the expected number of contacts relative to random seating, making the return to in-person classes more feasible under these scenarios.

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