Engineering Commons^™

Development Of Suspensions Adapted Vero Cell Culture Process For Production Of Viruses, Chun Fang Shen, Claire Guilbault, Mehdy Elahi, Sven Ansorge, Lakshmi Krishnan, Rénald Gilbert, Xiuling Li, Amine Kamen

Vaccine Technology VII

Vero cells are considered as the most widely accepted continuous cell line by the regulatory authorities (such as WHO) for the manufacture of viral vaccines for human use. The continuous Vero cell line has been commercially used, after propagation on microcarriers, for the production of rabies, polio, enterovirus 71 and hantaan virus vaccines. Vero cell culture technologies are also explored for productions of many more viral vaccines over the last two decades. The growth of Vero cells is anchorage-dependent, and cells need to be dissociated enzymatically or mechanically for the process of subcultivation. This process is labor intensive and complicated …

A Vaccine For Ebola Virus – Approaches And Results Of Accelerated Process Development And Characterization Studies, Randi Saunders, Joseph P Califano, Dusan Ruzic, Kristin Valente

Vaccine Technology VII

In 2014, West Africa experienced the worst outbreak of Ebola virus in history with 10 times more cases than in all previous outbreaks combined. In response to this public health emergency, MSD and a global network of partners collaborated to speed the research, development, and deployment of a candidate vaccine that ultimately provided the first evidence of efficacy in human subjects for any Ebola vaccine. While work continues to ultimately license the candidate vaccine, a risk-based approach to process development and characterization was used to accelerate and prioritize the study of parameters. Risk was evaluated by experts familiar with unit …

High-Titer Rapid Response Platform For Epidemic Preparedness, José Castillo

Vaccine Technology VII

Recent epidemics & pandemics have exposed serious flaws in global response to infectious disease outbreaks, as no vaccine were available to stop the diseases, due to limited market incentive.

New initiatives, such as the CEPI “Coalition for Epidemic Preparedness Innovations” are focusing on accelerating vaccine development for priority disease and ensuring their global availability.

In this light, Univercells is dedicated to designing novel biomanufacturing technologies to accommodate new products at short notice.

Univercells innovative manufacturing concept is designed to enable the rapid generation of potent vaccine candidates against a broad spectrum of targets, with the capacity to rapidly scale-up and …

Development Of A Vaccine Production Platform For Poultry Diseases In Africa: Newcastle Disease Virus Non-Replicative Adenovirus-Vectored Vaccine, Omar Farnos, Amine Kamen, Héla Kallel, Khaled Trabelsi, Martha Yami, Esayas Gelaye

Vaccine Technology VII

Poultry are a vital village livestock playing an important economic and nutritional role in the livelihoods of poor rural households in developing countries, including the Sub-Saharan Africa. Poultry production in Africa is threatened by infectious diseases such as Newcastle Disease (ND), which is highly contagious and endemic, with recurrent outbreaks that provoke heavy losses every year. ND is caused by the Newcastle disease virus (NDV), a negative-sense single-stranded RNA virus from the genus Avulavirus, family Paramyxoviridae. In particular, ND is one of the major problems in village chickens in most parts of Ethiopia where commercial poultry is routinely vaccinated …

Virus-Like Particle Vaccines Against Bk And Jc Polyomaviruses, Diana V. Pastrana, Alberto Peretti, Eileen M. Geoghegan, Christopher B. Buck

Vaccine Technology VII

Nearly all healthy adults are asymptomatically infected with human polyomaviruses. In immunosuppressed individuals, the infection can reactivate and cause disease. BK polyomavirus (BKV) frequently damages transplanted kidneys and causes severe bladder disease in bone marrow transplant patients. JC polyomavirus (JCV) causes a lethal brain disease, PML, in individuals on various immunosuppressive therapies. PML also affects immunodeficient individuals, including AIDS patients.

The outer capsid proteins of polyomaviruses are structurally similar to the capsids of human papillomaviruses (HPVs). Building on the success of the NCI’s HPV virus-like particle (VLP) vaccine technologies, we have developed VLP vaccines targeting BKV and JCV. Preclinical testing …

Conference Program, Amine Kamen, Tarit Mukhopadhyay, Charles Lutsch, Nathalie Garçon

Vaccine Technology VII

No abstract provided.

Membrane Chromatography Cassettes For Bind And Elute Applications Of Viruses And Large Proteins, Stefan Fischer-Frühholz, Martin Leuthold, Stefan Weisshaar, Florian Taft, Miyako Hirai, Amélie Boulais

Vaccine Technology VII

For flow-through polishing applications, membrane adsorbers have become a well-established technology. However, there is an increasing demand for bind and elute purifications for larger targets as adeno- and lentiviruses, virus like particles (VLP) and influenza. The reason is the higher binding capacity of macroporous membranes compared to conventional resins having much smaller pores and excluding them by size. But capture applications with such devices suffered from the current size limitation of 5 liters. Here we describe a modular cassette system which has been tested for scale-up and flow performance in comparison with void volume optimized capsules. The goals were to …

Influenza Virus Capture Using Membrane Chromatography: Improving Selectivity By Matrix Design And Pseudo-Affinity Ligand Interactions, Stefan Fischer-Frühholz, Florian Taft, Louis Villain, Amélie Boulais, R. Köhler, Sebastian Van Teeffelen, Michael W. Wolff, Udo Reichl, A. Raquel Fortuna

Vaccine Technology VII

Because next generation cell-based influenza vaccines have to be produced faster and in greater quantities than traditional vaccines, future purification processes will require more efficient unit operations for their isolation and purification. Membrane chromatography has already demonstrated a number of positive characteristics for the bind&elute purification of viral particles like e.g. adenoviruses or influenza viruses. The technology not only addresses the diffusion limitations of porous particle media but also offers dramatic advantages in binding capacity in a disposable format. Therefore, the last remaining challenge for the easy adoption of this technology in the vaccine industry represents selectivity and recovery. We …

An Outbreed Mouse Model Of Yellow Fever For Study Of Pathogenesis And Development Of Vaccines And Therapeutics, Yakhya Dieye, Moussa Dia, André Bedekelabou, Ousmane Faye

Vaccine Technology VII

Yellow fever (YF) is a mosquito-borne viral disease that is endemic in several African and South American countries. YF virus (YFV) causes subclinical infections with mild and non-specific symptoms, to severe, potentially lethal illness with jaundice, hemorrhage, and renal failure. Despite the existence of safe and efficient vaccines, epidemics continue to occur, mostly in Africa where the burden of YF is estimated to represent 1.7 million annual cases and up to 80,000 deaths per year. Moreover, emergence of YF has been reported in new, previously unaffected areas, because of the introduction of the mosquito vectors into these lands. There is …

Characteristics Of Rvsv-Zebov Production Kinetics In Hek293 And Vero Cells, Sascha Kiesslich, Amine Kamen, Jean-François Gélinas, Rénald Gilbert

Vaccine Technology VII

The vesicular stomatitis virus (VSV) can be used as an effective vaccine platform, inducing both cellular and humoral immunity. Because VSV infections of humans are mostly asymptomatic, recombinant VSV (rVSV) can be used as a platform to safely deliver and express foreign antigens. This research study focusses on cell culture production of an rVSV expressing the Ebola virus glycoprotein on its surface (rVSV-ZEBOV). This virus has been demonstrated to be safe to administer to humans. In addition, recent results of a human phase III clinical trial showed that this vaccine can efficiently protect against Ebola virus infection. However, limited data …

Disruptive Micro-Facility For Affordable Vaccine Manufacturing, José Castillo

Vaccine Technology VII

Univercells is offering disruptive manufacturing platforms based on innovative upstream and downstream approaches, aiming at increasing the availability and affordability of biotherapeutics.

The use of fixed-bed high-density bioreactors with sequential in-line clarification and capture operations creates an intensified and integrated process, resulting in a drastic reduction of footprint and capital expenditure.

By designing a flexible process that can easily be adapted to any viral vaccine without hardware modification, Univercells wishes to reduce the burden of developing adapted manufacturing processes for newly developed vaccines, facilitating their way towards commercialization.

With this process, viral vaccines such as polio can be produced in …

Conference Program, Millicent Sullivan, Josué Sznitman, Lola Eniola-Adefeso, Srivatsan Kidambi

Nanotechnology in Medicine II: Bridging Translational in vitro and in vivo Interfaces

No abstract provided.

Effect Of Recycled Geopolymer Concrete Aggregate On Strength Development And Consistence Of Portland Cement Concretes, Napoleana-Anna Chaliasou, Andrew Heath, Juliana Calabria Holley, Kevin Paine

Alkali Activated Materials and Geopolymers: Versatile Materials Offering High Performance and Low Emissions

Numerous studies have shown that production of geopolymer cement concretes can have lower carbon emissions compared to Portland cement concretes. However, for a full lifecycle assessment of environmental impacts, scenarios for the end of structures’ design life of must be considered, including reuse options. The work presented here is part of a wider study investigating the recyclability of fly ash-slag geopolymer cement (GC) concrete as an aggregate in Portland cement (PC) concretes.

Three types of GC concretes with varying Na₂O % per mass of precursor and SiO₂/Na₂O molar ratio were produced in the laboratory. …

Acid Geopolymer Materials Based On Different Aluminosilicate Sources, Sylvie Rossignol, Jenny Jouin, Virginie Mathivet, Michel Parlier

Alkali Activated Materials and Geopolymers: Versatile Materials Offering High Performance and Low Emissions

Geopolymers synthetized from the reaction of metakaolin (or alumino-silicate) in an alkali medium are studied since decades [1]. However, in order to develop composites, alkali medium is undesirable due to the detrimental effect of alkali ions on fibers. As an alternative, the use of an acid medium seems promising as some authors demonstrated an increase of mechanical properties with acid-based geopolymers [2, 3]. The aim of this work is to investigate the various formulations and to understand the reactional mechanisms.

The work is based on the activation of an alumino-silicate source with phosphoric acid to obtain geopolymer The various formulations …

Real Soils Versus Fake Soils: Does Something Other Than Clay Minerals Influence Geopolymerisation Behavior In Real Soils?, Alastair Marsh, Pascaline Patureau, Mark Evernden, Pete Walker, Andrew Heath

Alkali Activated Materials and Geopolymers: Versatile Materials Offering High Performance and Low Emissions

Uncalcined geopolymer-stabilised soils have shown potential for replacing concrete and fired clay as low carbon masonry materials. There is now a good fundamental understanding of how aluminosilicate precursors react to form geopolymer phases in simple systems, but there is a knowledge gap for the more complex systems of real soils where minor phases may influence behaviour. Because the clay minerals and their proportions differ between soils, as well as minor phases present, we are still not able to easily predict which soils are suitable for geopolymer stabilisation. In this study, a comparison was made for the alkali activation of real …

Investigation Of The Relationship Between The Condensed Structure And The Chemically Bonded Water Content In The Network Of Geopolymer Cements, Herve Tchakoute Kouamo, Sorelle J. K. Melele, Claus H. Rüscher, Elie Kamseu, Cristina Leonelli

Alkali Activated Materials and Geopolymers: Versatile Materials Offering High Performance and Low Emissions

The main objective of this work was to investigate the relationship between the condensed structure and the chemically bonded water content in the metakaolin-based geopolymer network. The kaolinite clay used in this work as an aluminosilicate source was transformed to metakaolin by calcination at 700 °C. The powder of the waste glass and the silica fume were used as silica sources for the synthesis of the hardeners. The obtained hardeners were characterized by infrared spectroscopy and MAS-NMR ²⁹Si. The metakaolin and the hardeners were used for producing geopolymers cements. The synthesized products were characterized by X-ray diffractometry, infrared spectroscopy, …

Analcime Geopolymers As Sorbents In Water Treatment, Hanna Runtti, Sari Tuomikoski, Janne Pesonen

Alkali Activated Materials and Geopolymers: Versatile Materials Offering High Performance and Low Emissions

Zeolite mineral, analcime [Na₁₆(Al₁₆Si₃₂O₉₆)·16H₂O], is formed in mining industry as lithium carbonate is produced from spodumene (LiAlSi₂O₆) using sodium pressure leaching process (1). Zeolite structure possess aluminosilicate framework and pores occupied by water and exchangeable cations (2). Zeolites act as cation exchangers due to which they have been applied as sorbents in water treatment (2). Geopolymers (GP) consist of an anionic framework of corner-sharing SiO₄ and AlO₄, and the exchangeable cations are located in the voids in the same way as in zeolites …

Performance Evaluation Of Metakaolin Clay Geopolymers Synthesised With Bamboo Wood Ash As An Activator, Mary B. Ogundiran, Olalekan P. Akinola

Alkali Activated Materials and Geopolymers: Versatile Materials Offering High Performance and Low Emissions

Global concern about substantial CO₂ emissions during manufacturing of Portland cement has led to studies on alternative low cost green binders. Geopolymer, an inorganic binder, which is produced from reaction of an alkaline activator and aluminosilicate mineral is receiving attention as an alternative cementitious material. However, one of the drawbacks of geopolymer production is the cost of chemical activators used in its synthesis. Studies are scanty on the use of Bamboo Wood Ash (BWA) as a less expensive alternative biomass ash activator in the synthesis of metakaolin clay geopolymers. Possibility of replacing a part of the alkaline commercial activator …

Investigation On Microstructure And Mechanical Properties Of Fa/Ggbs -Based Geopolymer After Exposure At Elevated Temperature, Apriany Saludung, Yuko Ogawa, Kenji Kawai

Alkali Activated Materials and Geopolymers: Versatile Materials Offering High Performance and Low Emissions

Fly ash (FA) and ground granulated blast -furnace slag (GGBS) are industrial wastes and have been widely utilized as construction material due to the environmental impacts. The use of these by-products is not only for the sustainable construction but also for reducing the emission of CO₂ due to the use of Portland cement. This study presents the microstructure and mechanical properties of geopolymer paste made from different ratios of low -calcium FA and GGBS after exposure at elevated temperature (500- 950^oC). Compressive strength tests for both heated and unheated cylindrical specimens (using 50 mm x 100 mm …

Geopolymers Including Cdw For Application As A Building Material, Matteo Panizza, Marco Natali, Adriana Bernardi, Matteo Panizza, Enrico Garbin, Michele Secco, Vilma Ducman

Alkali Activated Materials and Geopolymers: Versatile Materials Offering High Performance and Low Emissions

No abstract provided.

Conference Program, John L. Provis, Waltraud M. Kriven, Cristina Leonelli, Aldo Boccaccini, Arie Van Riessen

Alkali Activated Materials and Geopolymers: Versatile Materials Offering High Performance and Low Emissions

No abstract provided.

The Effect Of Cellulose Nanocrystals On Latex And Adhesive Properties In Emulsion- Based Polymer Nanocomposites, Marc A. Dubé, Emily D. Cranston, Carole Fraschini, Richard Berry

Polymer Reaction Engineering X (PRE 10) (2018)

Pressure sensitive adhesives (PSAs) adhere quickly and firmly to surfaces with the application of light pressure, and can be removed without leaving a residue. Their mechanical performance is measured by tack, peel strength and shear strength. A balanced combination between the three mechanical performance measurements depends on the specific end-use application and is challenging to achieve. This is particularly so when replacing solvent-based technologies with more sustainable, water-based (i.e., emulsion polymerization) technologies. PSAs synthesized using emulsion polymerization tend to have a lower shear strength due to poor gel network formation. As a result, conventional emulsion-based PSAs suffer from the inability …

Automatic, Simultaneous Control Of Molar Mass And Composition In Free Radical Copolymerization Using Acomp/Ci, Wayne F. Reed, Terry Mcafee, Thomas Zekoski, Aide Wu, Curt Jarand, Rick Montgomery

Polymer Reaction Engineering X (PRE 10) (2018)

ACOMP/CI has progressed to the point where molar mass and composition can be automatically controlled during free radical copolymerization reactions. The topics covered will be:

i) Automatic, simultaneous control of molar mass and composition in free radical copolymerization. The original strategy used to control only molar mass involved the use of two proportionality parameters, a_A and p, without any detailed kinetic models. a_A is monomer A conversion rate and p the link between instantaneous weight average molar mass M_w,inst and monomer concentration. a_A and p can be re-measured during a reaction as frequently as needed and …

Conference Program, John Tsavalas, Fouad Teymour, Jose R. Leiza, Jeffrey Stubbs

Polymer Reaction Engineering X (PRE 10) (2018)

No abstract provided.

More Accurate Process Understanding From Process Characterization Studies Using Monte Carlo Simulation, Regularized Regression, And Classification Models, Cary Opel, Cerintha J. Hui, Patrick Y. Yang, Daniel J. Tien, Gayle E. Derfus, Rajesh Krishnan

Cell Culture Engineering XVI

Establishment of an appropriate control strategy with defined operating ranges (OR) predicted to meet a target product profile is a critical component of commercializing new biologics under the Quality by Design (QbD) approach. Process characterization (PC) studies are performed to expand process understanding by achieving two main goals: 1) determining which process parameters have significant effects on quality attributes and 2) establishing models describing the relationships between these critical process parameters (CPP) and critical quality attributes (CQA). Risk assessment and design of experiments (DOE) techniques are effectively deployed in the industry to identify parameters to study and build process understanding. …

Advances In Cell Line Engineering And Protein Expression Strategies, Steven Lang, Diane Hatton

Cell Culture Engineering XVI

No abstract provided.

Cell Culture Bioprocess Learnings: Past Successes And Future Challenges, Günter Jagschies

Cell Culture Engineering XVI

Therapeutic proteins, vaccines and – further away – cell and gene therapies are considered essential to find efficacious interventions and preventive measures to a rather long list of prioritized needs in healthcare. The challenge is developing into a ‘tsunami’ of sorts as the global demographic transition causes populations to age, dramatically accelerating the growth of non-communicable disease (NCD) in all parts of the world. India and China are the markets with the largest patient population for almost any NCD, or they are going to be in that position soon. Competition in this field is ramping up with an intensity that …

Ipsc-Derived Neurospheroids Recapitulate Development And Pathological Signatures Of Human Brain Microenvironment, Catarina Brito, Ana Paula Terrasso, Daniel Simão, Francisca Arez, Marta M. Silva, Patrícia Gomes-Alves, Paula M. Alves, Marcos F. Sousa, Nuno Raimundo, Neus Bayó-Puxan, Sophie Creysells, Eric J. Kremer

Cell Culture Engineering XVI

Brain microenvironment plays an important role in neurodevelopment and pathology, where extracellular matrix (ECM) and soluble factors modulate multiple cellular processes. Neural cell culture typically relies on the use of heterologous matrices that poorly resemble the brain ECM or reflect its pathological features. We have previously demonstrated that perfusion stirred-tank bioreactor-based 3D differentiation of human neural stem cells (NSC) - pSTR-neurospheroids, sustains the concomitant differentiation of the three neural cell lineages (neurons, astrocytes and oligodendrocytes) and the establishment of physiologically relevant cell-cell interactions. Here, we hypothesized that if the pSTR-neurospheroid strategy would also allow the deposition of native neural ECM …

Mir-Catch Identifies Biologically Active Mirna Regulators Of The Pro-Survival Gene Xiap, In Chinese Hamster Ovary Cells, Paul S. Kelly, Alan Griffith, Sebastian Vencken, Nga T. Lao, Martin Clynes, Niall Barron

Cell Culture Engineering XVI

Genetic engineering of mammalian cells, in particular Chinese hamster ovary (CHO) cells, is of critical interest to the biopharmaceutical industry as a means to further boost the yields of therapeutic proteins. Complimentary to already in place advanced bioprocesses, stable overexpression of the pro-survival X-linked inhibitor of apoptosis (XIAP) is one example of the successful manipulation of CHO cell genetics resulting in prolonged culture survival, ultimately increasing recombinant protein productivity. However, saturation or burdening of the cells translational machinery can occur in instances of forced expression of a trans-gene thereby achieving the anticipated cellular phenotype without the associated improvement in productivity. …

Controlling Continuous High Cell Density Perfusion Culture With The Alternating Tangential Flow System In Real Time Using Radio-Frequency Impendance, Aditya Bhat

Cell Culture Engineering XVI

Many cGMP cell culture processes are now based on a continuous high cell density perfusion bioreactor system. Control of the feed or addition rates to maintain pseudo-steady-state conditions in these bioreactors can be especially challenging due to high and fluctuating cell concentrations that can rapidly change environmental conditions. With infrequent manual daily sampling based on offline cell counting, the control system can have too little information on which to base an appropriate decision to manipulate the process. Tight control of the perfusion or concentrate addition rate allows the bioreactor to be operated under the optimum conditions for maximum recombinant protein …