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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, …

Production Of A Fusogenic Oncolytic Rvsv-Ndv Virus In Perfusion Processes, Sven Göbel, Marie Dorn, Karim Jaén Chavez, Ingo Jordan, Volker Sandig, Jennifer Altomente, Yvonne Genzel, Udo Reichl

Vaccine Technology VIII

Oncolytic viruses (OVs), as a therapeutic vaccine, offer an elegant approach to cancer therapy. On the one side they have the ability to cause direct tumor cell lysis, on the other side they can stimulate immune responses directed against the tumor. By expressing endogenous or heterologous fusion glycoproteins, an enhanced intratumoral spread via syncytia formation can be achieved. Rapid and efficient fusion of infected cells may result in large multinucleated syncytia, in which cells quickly die before high titers are reached [1]. Prospective treatment with OVs will require manufacturing processes that enable the production of a very high number of …

Development Of A Standardized Multiplex Filovirus And Sars-Cov2 Antibody Immunoassay, Teri Ann S. Wong, Albert To, Axel Lehrer

Vaccine Technology VIII

With the goal of producing multivalent recombinant subunit filovirus and SARS-CoV-2 vaccines, we develop formulations using surface glycoproteins of Ebola, Marburg and Sudan viruses or the Spike protein of the SARS-CoV-2 virus. In determining the potency of our formulations in generating an immune response in mice and non-human primates (NHP), serum antibody titers are used. Instead of using conventional antigen-binding ELISA assays for each antigen, we conduct testing by a custom multiplex immunoassay. This method uses regionally different magnetic beads coupled to purified recombinant antigens which are incubated with serum dilutions to simultaneously determine the antibody titers to the different …

A Tale Of Two Worlds From The Ongoing Pandemic – Unprecedented Successes And All Too Familiar Failures, David Robinson

Vaccine Technology VIII

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Targeting Endogenous Retroviruses Using A Novel Adenoviral Vaccine Technology, Anne-Marie Andersson, Emeline Ragonnaud, Joana D. Boluña, Isabella S. Pedersen, Amaia V. Bermejo, Lasse Neukirch, Karen N. Nielsen, Silke Schroedel, Christian Thirion, Peter J. Holst

Vaccine Technology VIII

Human Endogenous Retroviruses (HERVs) are promising cancer vaccine targets as they are reactivated in cancers while being silent in healthy tissues. Around 8-9% of our genome is made up of HERVs and reactivation of HERVs, especially HERV-K, have been implicated in tumorigenesis via oncogenic signaling and immune evasion. As one of the means for cancer immune evasion, HERVs utilize an Immune Suppressive Domain (ISD) located in their envelope protein (Env). Here, our cancer vaccine strategy was to evaluate if adenoviral vaccines encoding a virus-like particle immunogen design including Gag for particle formation and an ISD mutated Env protein (ISDmut) as …

Development Of A Pneumococcal Conjugate Vaccine Drug Product: Ensuring Stability, A Robust Manufacturing Process And Long-Term Commercial Sustainability, William Smith

Vaccine Technology VIII

Successful development, commercialization and life cycle management of a vaccine drug product represents a significant challenge. For effective, broad-strain pathogen coverage, an antibacterial vaccine often contains multiple antigens formulated at low concentration in the presence of an adjuvant. Due to the complex nature of a vaccine drug product formulation, understanding how manufacturing, packaging, shipping, and storage temperature impacts the underlying physicochemical properties of the drug product is critical. Due to the complexity of the human immune system, if chemical or physical changes occur, comprehending how these changes impact clinical efficacy can be daunting. Therefore, efforts should be directed toward ensuring …

Bioanalytical Tools For The Quantification Of In-Process And Final Product Samples Of A Rotavirus Vaccine, Sofia B. Carvalho, Mafalda M. Dias, Jean-Philippe Matheise, Guillaume Van Beersel, Isabelle Knott, Patrícia Gomes-Alves, Paula M. Alves

Vaccine Technology VIII

Rotavirus A infection is a global leading cause of severe acute gastroenteritis associated with most of life-threatening diarrhoea episodes in infants and young children. However, the disease burden is being reduced namely due to wider access to rotavirus vaccines and their inclusion into National Immunization Programs of several countries. Besides being live-saving, rotavirus vaccination has an important economic impact, being cost-effective or even cost-saving in some countries. Nevertheless, vaccines are not yet routinely available in all countries. There is a demand to expand the rotavirus vaccination programs and improved analytical tools for high-throughput in-process product quality control and vaccine manufacturing …

Pre-Fabrication For Providing Biocapacity To Support Vaccine Manufacturing, Martin Birch, Thomas Hauser

Vaccine Technology VIII

The industry landscape is evolving rapidly and requires new and innovative approaches for more rapidly addressing the growing global demand for drug products as well as the challenges of unpredictability and inflexibility that have historically burdened the industry. Over the past two years, the industry’s herculean response to the COVID-19 pandemic has proven that with the proper focus, investment, science, and manufacturing technologies, these historic challenges can be overcome as well as establishing new benchmarks for how the industry can perform in the future to ensure availability of drug products and therapies to the global patient base

Prefabricated modular construction …

Rotavirus Vp6 Nanotubes Show An Antigen Form-Dependent Adjuvant Activity: Zika Virus Envelope Protein Monomer Vs Zika Virus-Like Particles, Arturo Liñan, Ana Ruth Pastor, Selene J. Uribe-Romero, Mabel Rodriguez, Octavio T. Ramirez, Laura A. Palomares

Vaccine Technology VIII

The structural protein of rotavirus (RV) VP6 can self-assemble into tubular polymeric structures under specific conditions of pH and ionic strength when expressed in recombinant systems. Previous studies have shown that RV VP6 nanotubes (VP6NT) have an adjuvant effect on the immunogenicity of norovirus virus-like particles (VLPs) in mice (Blazevic et al., 2011; Malm et al., 2016). The present study focused on the determination of adjuvant activity of VP6NT on the immunogenicity of monomers of the viral envelope (E) protein or of Zika virus (ZikV) VLPs. ZikV infection can cause congenital malformations in fetuses and the Guillain-Barré syndrome in adults, …

Development Of Two Monovalent Antivenoms Against Two Moroccan Viper Venoms– Daboia Mauritanica And Cerastes Cerastes, Naoual Oukkache, José Marcelino, Abderrahmane Maaroufi

Vaccine Technology VIII

Snake envenomation entails more than 5 million people bitten yearly, out of whom 100,000 died and more than 300,000 are permanently disabled. This prompted the World Health Organization to classify snake envenoming as a neglected tropical disease in 2017.

In North Africa, we have more than 400.000 cases of envenomation with 50 deaths per year. These numbers are underestimated with the Cerastes cerastes (Cc) and Macrovipera mauretanica (Mm)are the most medically important snake species.

To this day, the only medication for snake envenomation is immunotherapy. The lack of a specific antivenom against Cc and Mm venoms in North Africa, prompted …

Analytical Development To Support Manufacturing Of A Sustainable Vaccine Against Invasive Nontyphoidal Salmonellosis, Francesca Necchi, Francesco Citiulo, Maria Grazia Aruta, Federico Pippi, Antonia De Felice, Alessandra Acquaviva, Emilia Cappelletti, Vittoria Marchetti, Danielle Carson, Sophie Myhill, Luigi Sollai, Carlo Giannelli, Daniele De Simone, Caroline Vipond, Omar Rossi, Francesco B. Scorza, Anna M. Colucci, Rocio Canals

Vaccine Technology VIII

GVGH is developing a candidate trivalent Salmonella vaccine to fight invasive nontyphoidal Salmonellosis (iNTS) and typhoid fever, especially aimed for sub-Saharan Africa to impact disease burden and to reduce anti-microbial resistance spread. This trivalent vaccine may be the only viable option for a sustainable iNTS vaccine in sub-Saharan Africa over the separate administration of Typhoid Conjugate Vaccines (TCV) and a vaccine against iNTS.

GVGH generated the iNTS-TCV formulation by combining the GMMA technology for the iNTS components, S. Typhimurium (STm) and S. Enteritidis (SEn) GMMA adsorbed on Alhydrogel, and the Vi-CRM197 glycoconjugate, originally developed by GVGH and recently WHO prequalified …

Challenges And Opportunities To Formulate And Stabilize Vaccine Candidates Targeted For Use In Lmics, David Volkin

Vaccine Technology VIII

N/A

Please click Additional File below for the presentation.

An Adenovirus-Based Vaccine Manufacturing Technology Platform For Mucosal Or Parenteral Immunization Against Poultry Diseases In Sub-Saharan Africa, Omar Farnós, Esayas Gelaye, Samia Rourou, Alya Soudani, Khaled Trabelsi, Alice Bernier, Kumar Subramaniam, Martha Yami, Amine A. Kamen

Vaccine Technology VIII

Developing novel vaccine technology platforms to respond to emergency situations such as pandemic threats or zoonotic diseases is a worldwide high priority. Public health at a global scale is frequently influenced by the risk of transmission of infectious diseases from wildlife and domestic animals. Thus, veterinary vaccination and animal health monitoring are highly relevant for the deployment of a preventative global policy in the context of “one world, one health”.

In regions such as Sub-Saharan Africa, farmers’ activities are frequently affected by the impact of diseases in poultry such as avian influenza and Newcastle disease (ND). ND is one of …

This Is Our Shot - New Measures Of Vaccine Infectivity, Johanna Bacher

Vaccine Technology VIII

Whereas modern up- and downstream processes to produce viral vaccines are continuously optimized for high and pure viral titers, analytical methods to determine the infectious titer in a bulk, still lag. TCID50 and plaque assay are gold standard infectivity assays used in the industry, but only show results after 1-2 weeks and thus, hinder process control and development. They are operator-dependent, elaborate and furthermore, the particle content (measured by NTA) and the infectious particle content (measured by TCID50) do not go hand in hand. In this work, cytosolic Calcium, a ubiquitous element involved in all cellular processes is measured as …

The Inactivated Ndv-Hxp-S Covid-19 Vaccine Induces A Significantly Higher Ratio Of Neutralizing To Non-Neutralizing Antibodies In Humans As Compared To Mrna Vaccines, Juan Manuel Carreño, Ariel Raskin, Gagandeep Singh, Johnstone Tcheou, Hisaaki Kawabata, Charles Gleason, Komal Srivastava, Vladimir Vigdorovich, Nicholas Dambrauskas, Sneh Lata Gupta, Irene Gonzalez, Jose Luis Martinez, Stefan Slamanig, D. Noah Sather, Rama Raghunandan, Ponthip Wirachwong, Sant Muangnoicharoen, Punnee Pitisuttithum, Jens Wrammert, Mehul S. Suthar, Weina Sun, Peter Palese, Adolfo Garcia-Sastre, Viviana Simon, Florian Krammer

Vaccine Technology VIII

NDV-HXP-S is a recombinant Newcastle disease virus based-vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which expresses an optimized (HexaPro) spike protein on its surface. The vaccine can be produced in embryonated chicken eggs using the same process as that employed for the production of influenza virus vaccines. Here we performed a secondary analysis of the antibody responses after vaccination with inactivated NDV-HXP-S in a Phase I clinical study in Thailand.

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Automated Single-Cell Cloning In Chemically Defined Medium For New Suspension Mdck Cell Lines And Scale-Down Of Influenza A Virus Production Into Ambr®15 Microbioreactors, Tilia Zinnecker, Ilona Behrendt, Maverick Lau, Angelika Hinkelmann, Kristin Thiele, Najd Badri, Diogo Araujo, Yvonne Genzel, Udo Reichl

Vaccine Technology VIII

Vaccines for known and emerging diseases as well as new therapeutic applications of viruses will require multiple doses and high virus input per dose or treatment. Therefore, there is a clear need for innovation in vaccine manufacturing. Yet, process optimization and intensification are cost- and labor-intensive challenges and thus not always considered as economically reasonable. To tackle this problem and compete against outdated cost calculations, this work aims to transfer knowledge and techniques that were acquired within a decade of protein production process development into the field of viral vaccine manufacturing. This comprises the development of monoclonal suspension MDCK cell …

Immune-Profiling Of Innate And Adaptive Immunity Following Three Vaccinations Of The Mers Vaccine Candidate Mva-Mers-S, Christine Dahlke, Anahita Fathi, Leonie M. Weskamm, Bart L. Haagmans, Stephan Becker, Gerd Sutter, Marylyn M. Addo

Vaccine Technology VIII

Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by MERS coronavirus (MERS-CoV). In follow-up to a phase 1 trial, we performed a longitudinal analysis of immune responses following immunization with the Modified Vaccinia virus Ankara (MVA)-based vaccine MVA-MERS-S encoding MERS-CoV-spike protein. Three homologous intramuscular immunizations were administered on days 0 and 28 with a late booster vaccination at 12±4 months. Vaccination with MVA-MERS-S revealed a benign safety profile. No serious or severe adverse events were reported. Here, we analyzed innate and adaptive immune responses to the MVA-MERS-S in ten vaccinees. For this approach, blood samples were collected frequently …

Vaccine Manufacturing Capacity Expansion – An Approach To Meet Global Needs Based On Covid-19 Learnings, Julia Kuhn

Vaccine Technology VIII

COVID-19 has spurred the deployment of large sums of capital and major multilateral involvement in building vaccine manufacturing capacity in LMICs; however, manufacturing facilities will not be functional or sustainable without a skilled workforce to operate them. The Bill & Melinda Gates Foundation has developed a three-pronged approach to (1) Understand manufacturer needs; (2) Train via innovative and accessible materials; and (3) Build a sustainable ecosystem through linked initiatives.

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Development Of Analytical Characterization Tools For Process Monitoring Of Adenovirus-Based Vaccines (Chadox And Ad5), Shaleem I. Jacob, John M. Hickey, Andrew Tait, Fatemeh Dastjerdi Vahid, Sarah Rouse, Joseph Barritt, Alexander Douglas, Sangeeta B. Joshi, David B. Volkin, Daniel G. Bracewell

Vaccine Technology VIII

Product quality understanding is a critical part of viral vector vaccine manufacturing and regulation. Mass spectrometry is a technique that has widely been applied to protein-based therapeutics and could be used as a characterisation tool to monitor viral vector vaccine product quality. The ultimate objective of this Bill and Melinda Gates Foundation funded project is to enable vaccine manufacturing in Low and Middle-income countries (LMIC) through increased scientific understanding of viral vector vaccine manufacturing bottlenecks and therefore de-risking of vaccine development and manufacturing.

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Adenovirus-Based Vaccine Platform For Mucosal Or Parenteral Immunization Of Chickens, Omar Famos Villar

Vaccine Technology VIII

No abstract provided.

Development Of The Filamentous Fungus Thermothelomyces Heterothallica C1 Into A Next-Generation Production Platform For Human And Animal Vaccines, Ronen Tchelet, Marika Vitikainen, Noelia Valbuena, Anne Huuskonen, Abraham Nyska, Markku Saloheimo, Mark Emalfarb

Vaccine Technology VIII

engineering. The thermophilic fungus Thermothelomyces heterothallica is a robust and versatile fungal expression system for the rapid production of proteins at very high levels. In the last 6 years, the C1 protein production platform has been further improved to become a safe and efficient expression system with the prime objective of speeding up the development and production of commercial scale human and animal vaccines, monoclonal antibodies, biosimilars, as well as other therapeutic proteins at larger quantities and lower cost.

C1 is a very efficient platform to produce antigens, even to generate multicomponent vaccines. The production levels of engineered C1 strains …

Affinity Resins Enable A Multi-Vaccine/Platform Purification Process And Rapid Response To New Viruses, Warren Kett, Kent Hallenbeck

Vaccine Technology VIII

Established platform processes applicable to a range of recombinant sub-unit vaccines and VLPs will enable rapid response as well as easy adaption to seasonal variants. Affinity purification has the ability to provide a platform purification process affording a standard high purity, high yield purification step towards different vaccines. We describe several affinity resins that we have developed that enables this platform approach for different vaccine modalities, some of which can be considered custom affinity resins, whilst the others open access catalog resins.

The approach used is based on targeting elements or domains that are common to a vaccine technology and …

A Novel Sars-Cov-2 (T Cell) Vaccine Candidate Designed Using The Ivax Platform, Kirk Haltaufderhyde, Christine M. Boyle, Andres H. Gutierrez, Mayara Grizotte-Lake, Frances Terry, Bethany G. Mcgonnigal, Nicole Ruggiero, Leonard Moise, William D. Martin, Anne S. De Groot

Vaccine Technology VIII

EpiVax, Inc., a Rhode Island-based Biotechnology company, develops vaccines that exploit T cell immunity using the innovative iVAX vaccine antigen design platform. The premise of our strategy is the crucial role T cells play in development of protective antibody and cell-mediated immunity in natural infection. Because vaccines aim to recapitulate protective immune responses in infection, a vaccine should effectively harness T cell immunity to be protective. The significance of T cell immunity is underscored by COVID-19. Efficacy trial and real-world COVID-19 vaccine data for different vaccine modalities show a single vaccine dose is as much as 90% effective starting 14 …

Adapting Flublok/Supemtek® Recombinant Protein Expression Systems To Sars-Cov-2, Steven Hauser, Val Mermall, Nikolai Khramtsov, Ronald Neeleman

Vaccine Technology VIII

Sanofi co-developed a SARS-CoV-2 recombinant protein vaccine for the prophylaxis of COVID-19 disease based on recombinant protein antigens adjuvanted with AS03 from GSK. The recombinant protein used leverages the safe and effective platform used to produce Flublok/Supemtek® (Flublok), the first licensed recombinant seasonal influenza vaccine. The manufacturing process of Flublok utilizes a platform based on the baculovirus expression vector system (BEVS) for the expression of recombinant hemagglutinin (rHA) proteins in insect cells. Recombinant proteins in this system are expressed using a viral vector (baculovirus Autographa californica multinucleocapsid nuclear polyhedrosis virus) that is non-pathogenic to humans. Our cell line for protein …

Towards Updatable, Multivalent Covid Vaccines: A Platform Process To Produce Trimeric Spike Protein Of Sars-Cov-2 Variants Expressed In Hek293 Stable Cell Clones, Renata G.F. Alvim, Tulio M. Lima, Federico F. Marsili, Leda R. Castilho

Vaccine Technology VIII

Within 2.5 years since SARS-COV-2 emergence, COVID-19 pandemic has caused more than 6.3 million registered deaths and 530 million registered cases. The quick development of safe and effective vaccines was very important to mitigate the sanitary crisis. However, the continuous emergence of virus variants with increasing transmissibility continues to cause periodic outbreaks worldwide. The original vaccines keep protecting from severe disease and death caused by variants, but not from transmission and mild disease. Thus, new and improved vaccines are necessary, and updatable, multivalent pan-variant vaccines might be one way to control SARS-COV-2.

The spike (S) protein of SARS-COV-2, a highly …

Mutation Of A Conserved, Hydrophobic, Cryptic Epitope Improves Manufacturability And Immunogenicity Of The Sars-Cov-2 Rbd, Sergio Rodriguez Aponte, Neil C. Dalvie, Ting Y. Wong, F. Heath Damron, J. Christopher Love

Vaccine Technology VIII

The supply of COVID-19 vaccine doses still lags behind the global demand for first time vaccination and booster doses. Distribution of vaccine doses has been far from equitable across the world given the steep prices and logistical challenges that low- and middle-income countries face. Subunit protein vaccine candidates have now been shown to elicit protective responses against SARS-CoV-2 infection, while providing additional benefits for manufacturing capability and stability requirements compared to many currently approved vaccines. Here we report a second-generation engineered RBD sequence variant with enhanced manufacturability and immunogenicity over the wild-type ancestral RBD and a first-generation engineered variant (RBD-L452K-F490W …

Genetically Detoxified Diphtheria And Tetanus Toxins, Ecocrm197® And 8mtt, Expressed In An Engineered E. Coli Strain And Use As Conjugate Vaccine Carrier Proteins, Andrew Lees, Morgane Ollivault-Shiflett, Min-Ju Chang, Renaud Jacquemart

Vaccine Technology VIII

We have developed a novel E. coli expression system, which we call the Gor/Met strain. Gor/Met E. coli has an oxidative cytoplasm and can express disulfide-bonded proteins as intracellular, soluble, properly-folded proteins. In addition to the oxidative cytoplasm, the strain has been engineered to efficiently cleave the N-terminal methionine found on cytoplasmic E. coli proteins. To create an oxidative cytoplasm, we deleted the gor gene in BL21 E. coli, resulting in an oxidative cytoplasm. We used the gor- strain to produce the conjugate vaccine carrier protein CRM₁₉₇ in a fermenter. CRM₁₉₇ was expressed as a soluble, properly …

Enabling Technologies For Manufacturing Thermostable And Cost-Effective Vaccines, Justin Stanbro, Akhilesh Bhambhani, Morrisa Jones, Donna Williams, Jeffrey T. Blue, Tarit Mukhopadhyay

Vaccine Technology VIII

Biopharmaceuticals are often intrinsically unstable and can rely on freeze-drying as a standard approach for stabilization. Although a standard, this process has long cycle times, is a batch drying process, and is incompatible with flexible manufacturing. There is need for advancing novel approaches that enable the vision for “a maximally efficient, agile, flexible, manufacturing sector that reliably produces high-quality drug products without extensive regulatory oversight;” (2004, FDA Pharmaceutical Quality for the 21st century).

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Disease X Development And 100 Days Initiative, Nicolas Havelange

Vaccine Technology VIII

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Producing Viruses In Orbit: Current Developments For Orbital Shaken Viral Vaccine Manufacturing, Tim Bürgin, Juliana Coronel, Katharina Fiddeke, Volker Sandig, Yvonne Genzel, Udo Reichl, Tibor Anderlei

Vaccine Technology VIII

Preculture of suspension cells is successfully performed in shake flasks. Especially newly developed designer cells are passaged up to 100 times in shake flaks at high shaking frequency and are then perfectly adapted to growth in a CO₂ incubator with pH control and maximum oxygen supply (typically above 80% pO₂). When they are subsequently transferred to stirred tank bioreactors for scaling up, specific cell growth rates are often lower and cells become sensitive to pH control via acid/base addition and shear stress due to submers gassing (bubbles). This was also seen for avian AGE1.CR.pIX and human HEK …