Digital Commons Network^™

Intensification Of Influenza Virus Production In Fed-Batch And Perfusion Cultures Of Hek293sf Cells, Cristina A.T. Silva, Amine A. Kamen, Olivier Henry

Vaccine Technology VIII

More than half a million people die every year from complications of seasonal influenza, and vaccination stands as the most effective method to prevent and limit outbreaks of the disease. Constant vaccine development based on emerging strains and worldwide distribution of vaccines is a great challenge for public health and vaccine manufacturers, particularly in a potential pandemic scenario. The limited flexibility of the current egg-based production system combined with recent advances in large-scale cell culture techniques have encouraged the development of cell culture processes for influenza vaccine production. While cell culture offers a valuable alternative, productivities are still low when …

Workshop: Innovation In Global Health, Birgitte Giersing, Marion Menozzi-Amaud

Vaccine Technology VIII

Vaccination is considered the most successful healthcare initiative in disease prevention, but achieving universal coverage is still beyond reach. According to the WHO, 19.4million did not receive routine life-saving vaccinations in 2018 – many of them children. To address this issue, research from both academia and industry partners are required to provide innovative solutions to problems in Global Health. This workshop will focus on the needs for the Global Health community and will be sub-divided into two sessions. The first session will provide examples of innovative solutions for persons in low and middle income countries, that seek to aid the …

Development Of An Automated Microscale Platform For Conjugate Vaccine Production In E. Coli, Jasmin J. Samaras, Martina Micheletti

Vaccine Technology VIII

The current state-of-the-art for the production of glycoconjugate vaccines is a lengthy and complex series of process steps. An exciting alternative is Protein Glycan Coupling Technology (PGCT), where glycoconjugates are produced in vivo ^1,2. This offers a significant reduction in the time and cost burden of glycoconjugate production, making this technology much more feasible for providing vaccines in developing countries. Current research seeks to apply this technology for pneumococcal vaccines ², however much process optimisation must be done before this is achievable. This work seeks to provide an automated screening platform at the microscale, enabling the rapid screening …

Genomics Of Vero Cells: Understanding This Cell Line And Its Virus-Host Interactions For Improved Vaccine Production, Marie-Angelique Sene,, Sascha Kiesslich, Haig Djambazian, Ioannis Ragoussis, Yu Xia, Amine A. Kamen

Vaccine Technology VIII

The Vero cell line is the most used continuous cell line for viral vaccine manufacturing with more than 40 years of accumulated experience in the vaccine industry. Additionally, the Vero cell line has shown high affinity for infection by MERS-CoV, SARS-CoV and recently SARS-CoV-2, emerging as an important discovery and screening tool to support the global research and development efforts in this COVID-19 pandemic.

Furthermore, Vero cells anchorage-dependent use renders scaling-up challenging and operations very labor intensive which affects cost effectiveness. Thus, efforts to adapt Vero cells to suspension cultures have been invested but hurdles such as the long doubling …

Advances In Therapeutic Hiv Vaccine Development, Christian Brander

Vaccine Technology VIII

N/A

Please click Additional File below for the presentation.

United States Subnational Flags: Flags Of Territories, States, Counties And Municipalities. Flags Of Native Americans Reservations, Rolland Mcgiverin

Library Faculty and Staff

No abstract provided.

Rapid And High Yield Microbial Protein Production System For Human And Animal Vaccines: C1 Filamentous Fungus Thermothelomyces Heterothallica, Noelia Valbuena

Vaccine Technology VIII

N/A

Production Of Influenza A Virus Defective Interfering Particles In A High Cell Density Perfusion Cultivation With Continuous Virus Harvesting, Marc D. Hein, Anshika Chawla, Prerna Arora, Maurizio Cattaneo, Michael Winkler, Stefan Pöhlmann, Klaus Schughart, Yvonne Genzel, Sascha Y. Kupke, Udo Reichl

Vaccine Technology VIII

Causing annual epidemics and occasional pandemics, influenza A virus (IAV) is a human pathogen that has severe impact on health and society. Defective interfering particles (DIPs) have been discussed as a potential antiviral therapeutic [1]. Most IAV DIPs are naturally occurring viral mutants harboring large internal deletions in at least one of their eight viral RNA (vRNA) segments. Due to these deletions, DIPs can only replicate in the presence of infectious standard virus (STV), compensating for the missing gene function. In a co-infection, the defective vRNA segment interferes with STV genome replication, which is causative for the therapeutic potential of …

Model-Based Process Development For Complex Vaccine Mixtures, Daphne Keulen, Roxana Disela, Geoffroy Geldhof, Olivier Le Bussy, Martin Pabst, Marcel Ottens

Vaccine Technology VIII

The regulations, safety and purity demands are extremely high for vaccine processes and likewise reflected in process development time and cost. Reducing time-to-market is key for pharmaceutical companies, hence saving lives and money, and therefore the need raised for systematic, general and efficient process development strategies (Hanke & Ottens, 2014). Despite the tremendous variation between vaccine purification processes, platform processes for similar types of vaccines could aid to generally accelerate the process development and would be beneficial in terms of knowledge, resources, costs and regulatory aspect. High throughput process development (HTPD) approaches can be used to establish platform processes. HTPD …

Design Of Mimotopes Of A Conserved Epitope In Dengue And Zika Viruses For The Obtention Of Broadly Neutralizing Antibodies, Esmeralda Cuevas-Juárez, Arturo Liñan, Carolina Hernandez, Mykhailo Kopylov, Laura A. Palomares

Vaccine Technology VIII

Zika and dengue viruses are members of the Flavivirus genus that share many structural and pathological characteristics. They cause mild fever, rash and general body pain but can cause severe reactions, as hemorrhages (dengue virus), congenital syndrome (Zika virus), or even death. After an infection, virus-specific antibodies are generated by the immune system; however, because of the structural similarity between these viruses, some antibodies can cross-react with different members of the flavivirus family. After a secondary infection, the cross-reactive antibodies can lead to the more severe forms of the disease, through a mechanism named antibody-dependent enhancement of infection (ADE). Recently, …

Protein Design And Immunogenic Analysis Of Covid-19 Vaccine Candidates Based On Rbd/Trimeric-Spike Antigens And Chimeric Vlps Antigens, Claudio Prieto, Ernesto Garay, Javier Villarraza, Antonela Fuselli, Agustina Gugliotta, Celeste Rodríguez, Victoria Gastaldi, Natalia Ceaglio, Diego Fontana

Vaccine Technology VIII

Spike glycoprotein (S) and its Receptor Binding Domain region (RBD) are the main targets of neutralizing antibodies during an infection with SARS-CoV-2, the etiologic agent of COVID-19 pandemic viral disease. Thus, they are the chosen antigens for the development of diagnostic kits and vaccines candidates. Furthermore, Virus-like Particles (VLPs) constitute potent immunogens that have been engineered to obtain vaccine candidates through expression of SARS-CoV-2 S, M, E and N proteins. Although it might be a challenging platform, as multiple proteins must be expressed in order to assure VLP budding, they are able to induce stronger immune responses than soluble antigens …

High Density Hek293t Culture For High Yield, High Quality, Stable Adenoviral Vector Production In Ambr® 250 Stirred Tank Reactors, Amélie Boulais, Lara Nascimento-Brooks, Shuangqing Yu, Zhicheng Cao, Li Hu, Shuren Feng, Jinlu Du, Cuiling Song, Junjie Luo

Vaccine Technology VIII

Adenovirus vectors (AdV) present high safety and immunogenicity for drug development, allowing more and more vaccines to adopt this technology platform in recent years. Due to the current COVID-19 pandemic, the global demand for AdV has experienced significant growth. Therefore, to optimize the upstream process in order to obtain high yields, good quality and stable viral vectors, it becomes critical that processes are stable and easy to scale-up, which has become a key focus of pharmaceutical companies in the field.

Please click Download on the upper right corner to see the full abstract.

Development Of An Innovative Adenovirus-Inspired Self-Assembling Vaccine Platform Rapidly Adaptable To Coronaviruses And Other Emergent Viruses, Christopher Chevillard, Axelle Amen, Solène Besson, Dalil Hannani, Isabelle Bally, Valentin Dettling, Salomé Gallet, Emilie Stermann, Guy Schoehn, Evelyne Gout, Daphna Fenel, Marlyse Buisson, Christophe Moreau, Pascal Poignard, Marie-Claire Dagher, Pascal Fender

Vaccine Technology VIII

The COVID-19 pandemic clearly shows how emergent diseases can cause severe global health and economic problems. We must be prepared to react swiftly against new pathogenic agents and this requires the development of vaccines that are safe, efficient in the long-term and easily adaptable with a short revision time. To this end, the COVID-19 mRNA and adenoviral vector vaccines have been spectacular successes, permitting rapid vaccination across the world in an unprecedented manner. Here we report the design of a new adenovirus-derived vaccine technology based on non-infectious pseudo-viral nanoparticles from the serotype 3 human adenovirus. Each nanoparticle comprises sixty identical …

Chromatographic Tools For Optimization Of Ivt Reaction And Improving Mrna Purification Process, Amélie Boulais, Rok Sekimik, Kristina S. Nemec, Janja Skok, Klemen Božič, Anže Martinčič Celjar, Pete Gagnon, Aleš Štrancar

Vaccine Technology VIII

The recently demonstrated efficacy of mRNA-based Covid-19 vaccines has shown the promise of this therapeutic format, but also highlighted the need for higher efficiency of mRNA production to meet enormous needs for global vaccine supply.

Typical mRNA production process involves three key steps: 1) plasmid DNA (pDNA) production in supercoiled (sc) isoform, linearization and purification, 2) in-vitro transcription (IVT) reaction and 3) mRNA purification.

Here we present a chromatographic toolbox for integrated mRNA production from pDNA to mRNA purification, including in-process analytics.

The pDNA purification approach presented here was designed to fit the specific requirements of mRNA vaccines. It integrates …

Shifting The Paradigm From Global To National: Innovative Approaches For Sustainable Production Of Priority Vaccines, Birgitte Giersing

Vaccine Technology VIII

No abstract provided.

Optimisation Of An Alkaline Lysis Process For A Plug- And Play Plasmid Dna Production, Fatma Almulla, Eli Keshavarz-Moore

Vaccine Technology VIII

Renewed interest in plasmid DNA (pDNA) production is the result of its role in the supply chain of novel biopharmaceuticals.” pDNA lies at the heart of viral and mRNA vector production because it provides the coding sequences for gene-based advanced therapy medicinal products (ATMPs). Its manufacture is therefore critical to both the supply and success of these products”^1.

One main bottleneck in processing of pDNA is the lysis step that still rely on techniques developed for laboratory-based DNA extraction. A robust process adaptable to a range of DNA sizes and scales remain to be fully realised. These include control …

Suspension Vero Cell Culture Technology For High Titer Production Of Viral Vaccines, Chun Fang Shen, Rénald Gilbert, Elodie Burney, Seyyed Mehdy Elahi, Stephane Lanthier, Amine Kamen, Martin Loignon

Vaccine Technology VIII

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, hantaan, more recent COVID19 and other vaccines. Vero cell culture technologies were 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 …

Advancing Vaccine Development And Manufacture In Africa, Ebrahim Mohamed, Patrick Tippoo

Vaccine Technology VIII

Emerging and known infectious diseases pose a constant threat to the health and prosperity of Africa and its people. Africa, like other regions of the world with a high burden of vaccine preventable diseases, has benefited immensely from vaccines and Africa’s growing population means an increase in the continuing need for vaccines. By 2050, Africa’s population will be 2.5 billion and one in four people in the world will be African.

However, Africa has limited capacity to produce vaccines, yet is the most in need of routine vaccines. Currently less than 1% of vaccines used in Africa is made in …

A Versatile Capillary Gel Electrophoresis Methodology For In-Process And Final Product Characterization Of Virus-Based Targets, Rita Fernandes, José Escandell, Filipa Moura, Ana C.L. Guerreiro, Sofia B. Carvalho, Tiago Q. Faria, Ricardo J.S. Silva, Patrícia Gomes-Alves, Cristina Peixoto

Vaccine Technology VIII

The biopharmaceutical industry is approaching a turning point where new therapeutic modalities such as virus-based biopharmaceuticals are used in several applications such as vaccination, gene therapy and oncolytic therapy. However, the bioprocess of functional viruses still presents challenges, namely due to the availability of suitable analytics for downstream processing monitoring or characterization of the final product. Capillary electrophoresis (CE) is a versatile technique that enables the determination of intact or reduced particle number and the quantification of several product-related impurities, such as host cell DNA and host cell proteins. Although this f platform is commonly used for purity profiling of …

A Universal Influenza B Vaccine Using Mosaic-Hemagglutinin Vaccine Candidates, Irene González-Domínguez, Yonghong Liu, Eduard Puente-Massaguer, Nicholas Lemus, Stefan Slamanig, Tsoi Ying Lai, Shirin Strohmeier, Madhumathi Loganathan, Jose Martínez-Guevara, Florian Krammer, Adolfo García-Sastre, Peter Palese, Weina Sun

Vaccine Technology VIII

Influenza viruses undergo antigenic changes in the immuno-dominant hemagglutinin (HA) head domain, necessitating annual re-formulation of and re-vaccination with seasonal influenza virus vaccines for maintaining the protection. We previously synthesized mosaic HA (mHA) proteins of influenza B viruses which redirect the immune response towards the immuno-subdominant conserved epitopes of the B virus HA via sequential immunization. As ~90% of current influenza virus vaccines are manufactured using the inactivated virus platform, we generated and sequentially vaccinated mice with inactivated influenza B viruses displaying either the homologous (same B HA backbones) or the heterologous (different B HA backbones) mosaic HAs. Both approaches …

Biomanufacturing Technology Advances Enable Rapid Response To Disease Outbreaks, Tania Pereira Chilima, Marie Jourdan

Vaccine Technology VIII

Outbreaks can have devastating socio-economic and mental health impacts if the spread of disease is not stopped. Particularly in the case of COVID-19 which has claimed thousands of lives across the globe, the importance of rapid response to disease outbreaks is paramount. In the past, response to pandemics was following very long licensing and development timeframes, whereas in the case of COVID-19 the response was immediate while approval and manufacturing timeframes were much shorter. The global COVID-19 pandemic has highlighted the important role that scalable and flexible manufacturing solutions play in enabling rapid response to new disease outbreaks. In this …

Use Of Sulfated-Cellulose Membrane Adsorbers To Intensify Purification Of Cell Culturederived Influenza A And B Viruses, Amélie Boulais, Ricarda Busse, A. Raquel Fortuna

Vaccine Technology VIII

New generation of cell culture-based vaccines enables faster response to pandemic outbreaks and helps coping with the increasing demand for seasonal vaccines. Besides efficient upstream processing technologies, appropriate economic and robust downstream processing is key to consistently achieve high yields. Chromatography membranes have been extensively evaluated to capture viruses at laboratory scale, for influenza, adenovirus or virus like particles. They have shown great potential to intensify processes thanks to a high binding capacity, high flow-rate and ease of use and are now commonly used in new generation of vaccine processes. We present here Sartobind SC, a novel sulfated cellulose membrane …

Acceleration Of Vaccine Development By Improvement Of Process Understanding - Analysis Of The Host Cell Proteome, Roxana Disela, Daphne Keulen, Geoffroy Geldhof, Olivier Le Bussy, Martin Pabst, Marcel Ottens

Vaccine Technology VIII

While regulatory agencies require stringent product quality and safety to be upheld in biopharmaceutical products, today’s competitive biopharmaceutical market requires short process development times. The demand to accelerate especially the development of vaccines became obvious with the COVID-19 pandemic. By expanding process understanding with the use of process design tools the development time of the purification could be significantly shortened.

High throughput experimentation (HTE) provides an automated experimentation platform, which minimizes the amount of used samples and saves experimental time. In this approach, HTE is used to acquire experimental data to regress parameters used as inputs for a chromatographic mechanistic …

Biophysical Technologies In Vaccines, Hervé Ponceblanc, Marco Garrido Sergio, Stephanie Prizzon

Vaccine Technology VIII

Vaccine safety, in agreement with different countries pharmacopeia, requires characterization and identification of the intrinsic and extrinsic particles nature when occurring at any step of production. It also covers eventual customer complaints and health authorities concerns. To efficiently achieve these tasks, pharmaceutical companies need to have a laboratory specialized in biophysical technologies for particle characterization. As in many cases intrinsic and extrinsic particles of identical nature are recurrent issues, an efficient recording of historical troubleshooting resolution will speed their characterization and identification. This requires the set-up of an in-house biophysical laboratory. In addition, ensure the comparability of raw materials and …

Optimization Of Rad5 Vectored Newcastle Vaccine Production In Hek293 At High Cell Densities, Samia Rourou, Amani Chaaben, Alya Soudani, Meriem Ben Zakour, Omar Farnós, Esayas Gelaye, Martha Yami, Amine Kamen, Khaled Trabelsi, Héla Kallel

Vaccine Technology VIII

Newcastle disease (ND) is a highly contagious and often severe global spread syndrome that affects birds including domestic poultry. It is caused by a virus belonging to the paramyxoviridae family.

Indeed, an outbreak of ND can be quite severe, and is considered as a constant threat to the industry and food security worldwide. The disease can be controlled through the administration of effective vaccines.

Immunizations with inactivated or live vaccines, although protective, have some eminent disadvantages.

The aims of this work is the development of a vectored vaccine using a non-replicative human adenovirus vector, expressing the F antigen from Newcastle …

Development Of A Purification Process For Hiv-1 Vlps, From Supernatant To Lyophilization, Elianet Lorenzo Romero, Laia Miranda, Irene González-Domínguez, Francesc Gòdia, Laura Cervera

Vaccine Technology VIII

HIV-1-based virus-like particles (VLPs) have high potential as scaffold for the development of chimeric or multivalent vaccines by functionalizing them with specific antigens [1], [2]. The obtention of vaccine formulations independent of cold chain is desirable to facilitate transportation and administration worldwide [3]. Recently, efforts are being made to develop cost-effective scalable processes to obtain these particles. The present study aims to compare some of the most used downstream processing (DSP) technologies for capture and purification of VLPs, taking especial consideration in using technologies enabling operation at large scale [4]. First, suspension adapted HEK 293 cells cultured in chemically defined …

Discovery & Development Of Therapeutic Interfering Particles (Tips): Single-Administration Sars-Cov-2 And Hiv Antivirals With High Barriers To The Evolution Of Resistance, Leor Weinberg

Vaccine Technology VIII

N/A

Towards A Virus Production Platform Based On Veros Cells Grown On Chemically Defined Media, Samia Rourou, Ikram Ben Marzouk

Vaccine Technology VIII

Vero cells are nowadays widely used in the production of vaccines. However, they are anchorage dependent, which greatly complicates upstream processing and process scale-up. Moreover, there is a recognized need to reduce the costs of vaccine manufacturing to develop vaccines affordable worldwide. The use of cell lines adapted to suspension growth contributes to reach this objective. We had previously adapted Vero cells to suspension growth for rabies virus (strain LP2061) production in different serum free media (Rourou et al. 2019).

In this work, we describe the use of a chemically defined medium (CDM) provided by Xell AG to assess the …

Impact Of Africa-Based Manufacturing On Cost-Per-Dose: A Theoretical, Inside-Out Analysis, Casey Selwyn

Vaccine Technology VIII

The inequitable rollout of COVID-19 vaccines has drawn global attention to the lack of vaccine manufacturing capacity in Africa. The Bill & Melinda Gates Foundation has conducted three analyses to better understand resourcing and market implications of manufacturing at different locations in Africa. This includes (1) a review of market dynamics and selection of three vaccines for deeper analysis; (2) an analysis of the cost-per-dose of vaccines produced at different locations in Africa versus a baseline in South Asia; and (3) an assessment of the market health knock-on effects of potential new entrants. Toggling variables had a range of impacts, …

Early Depression Screening And The Effects On Postpartum Depression, Tara Udy

Master of Science in Nursing Family Nurse Practitioner

Postpartum depression is as common as 3-22% of women. More and more studies are finding that one of the leading risk factors for postpartum depression is perinatal depression. With early screening during pregnancy, these women can be referred to proper treatment early and may reduce the risk of poor prenatal outcome for the patient and the baby. Use of the internet and mobile phone applications can make early screening easy and quick, using the EPDS as the gold standard for perinatal depression screening.