Biomedical Engineering and Bioengineering Commons^™

After The License Approval: How Analytics Can Keep You In The Market, Robert Sitrin

Vaccine Technology III

Getting a BLA approved for a new vaccine can be a daunting task, but keeping the market supplied after licensure of a successful vaccine can be an even bigger challenge. Analytics can play an important role in keeping product supplied to the marketplace, especially during the critical launch phase The talk will describe the application of analytical comparability to GARDASIL®, Merck’s novel new vaccine to prevent cervical cancer, in order to bridge product produced by a launch facility to that produced by a scale-up facility without the need for a clinical trial. This effort assured a smooth transition of supply …

Nipah/Hendra: Understanding The Links Between Human And Veterinary Emerging Diseases, Jules Minke

Vaccine Technology III

Animals constitute an important source of infectious diseases for humans and the majority of recent emerging diseases in humans are zoonotic. Infections occur through direct or indirect transmission from wildlife reservoirs or via the food chain. Nipah and Hendra viruses have recently joined the growing list of viruses that emerged from bats to cause serious disease in humans and livestock. Although the precise mode of virus transmission is not fully understood, human infection appears to be the result of close contact with infected horses and pigs that act as amplifying hosts. Improved control strategies are necessary to reduce the transmission …

Development Of Protein Capsular Matrix Vaccine (Pcmv) Technology, Kevin P. Killeen, Ann Thanawastien, Tom Griffin

Vaccine Technology III

Matrivax R&D Corp. is a start-up biotechnology company with R&D operations located in Boston, USA and a vaccine pilot facility in Haikou, China. We are developing a proprietary vaccine process that entraps polysaccharides in a cross-linked protein ‘carrier’ or matrix, termed Protein Capsular Matrix Vaccine (PCMV), as an alternative to conjugate vaccine technology. Despite highly efficacious pneumococcal vaccines such as Prevnar®, S. pneumoniae causes > 1 million deaths worldwide annually. Likewise, typhoid fever afflicts ~16 million people, resulting in 600,000 deaths despite effective vaccines such as Typhim Vi® and Ty21a. The premise is that inexpensive,efficacious polysaccharide vaccines that elicit TH-cell ‘memory’ …

Rabies Virus Glycoprotein (Rvgp) Expression In Drosophila S2 Cells And By Semliki Forest Virus (Sfv). Synthesis And Protection Studies, Carlos Pereira

Vaccine Technology III

Here we report the utilization of Drosophila melanogaster Schneider 2 (S2) cells and the Semliki Forest Virus (SFV) expression system to produce the rabies virus glycoprotein (RVGP). Although they represent different expression systems, they offer similar advantages in generating high-level expression of functional membrane proteins. They are both relatively easy and safe to handle and are scalable. RVGP synthesized by S2 cells and SFV carrying an mRNA coding for RVGP (SFV-RVGP) were assayed in mouse protection studies. We have constructed S2 gene vectors with the hygromycin selection gene (H) in which the RVGP gene is inserted under the control of …

Human Cells For Prostate Cancer Vaccine Therapy - The Impact Of Centrifugation Upon Key Product Quality Attributes, Michael Delahaye, Katherine Lawrence, Carol Chu Mike Hoare, Stephen Ward

Vaccine Technology III

Centrifugation is a unit operation used within a wide range of bioprocesses, including the production of a whole cell cancer vaccine to treat Hormone Refractory Prostate Cancer (HRPC) which has been tested in Phase II clinical trials. To quantify the effect of centrifugation-related stresses upon a whole cell vaccine population, a design of experiments (DOE) based investigation at micro-scale was implemented. Qualification of the cells may be by membrane integrity and by surface marker density as well as cytokines released and retained during bioprocessing. These and possibly other factors combine to affect the biopotency of the cells and their clinical …

Challenges In Confronting Pandemic Influenza Using Novel Adjuvanted Vaccines, Louis F. Fries

Vaccine Technology III

Pandemic influenza is a recurring threat throughout history. Characterized by rapid spread and high attack rate, the features of pandemic influenza are grounded in the lack of immunologic experience with pandemic virus subtypes in the majority of the human population alive during the outbreak. Immunization is regarded as a key tool in preparing for, and mitigating, pandemic influenza. Unfortunately, capacity to manufacture sufficient inactivated influenza antigen by currently-licensed processes remains challenging, and this problem is amplified by the very short timeline for production and distribution that may be available. GSK has addressed the pandemic influenza challenge by application of the …

Development Of A Multi-Dose Formulation For Prevnar 13™, Lakshmi Khandke, Cindy Yang, Jingrun Fan, Hanyoung Han, Ksenia Krylova Abbas Rashidbaigi, Bruce A. Green, Kathrin U. Jansen

Vaccine Technology III

Streptococcus pneumoniae causes up to a million cases per year of invasive disease in young children and infants, most occurring in developing countries. Pfizer is partnering with WHO and the GAVI alliance to support the developing world on immunization against pneumococcal disease. Prevnar 13™ is currently approved for the prevention of invasive pneumococcal disease in twenty seven countries. If used widely, this pneumococcal conjugate vaccine could prevent hundreds of thousands of additional cases of child mortality each year.

Use of single-dose preservative-free vaccine formulations will raise the overall cost of vaccination programs and may jeopardize the effectiveness of immunization programs …

Purification Process Development Of Protein Subunit Based Vaccine Candidates Produced Using Recombinant E. Coli Expression System (Part - I), Davinder Chawla, Yan-Ping Yang

Vaccine Technology III

Proteins are key components of prophylactic vaccines against infectious diseases. Protein subunit based vaccine is an attractive alternative to the traditional detoxified bacterial or inactivated viral vaccine approach due to its highly purified and well characterized product nature. Purification of protein antigens to achieve consistent product purity and quality is an integral part of the protein subunit vaccine product development process. Expression levels of the recombinant proteins in bacterial expression system may be extremely high following rapid technology advancement. The challenges and approaches used to develop purification processes for novel protein vaccine candidates expressed at g/L level will be discussed.

Innovative Therapeutic Cancer Vaccines In Cuba: An Update, Luis Enrique Fernández

Vaccine Technology III

Worldwide cancer affects more than 10 million new people each year while other 22 million are living with this devastating disease.

Cancer vaccines are the newest weapon in the battle against this disease, specifically increasing body's natural abilities to halt tumour progression. Currently, 141 distinct projects are at different stages of clinical development.

The Cuban Biotech System of Institutions has been actively involved in this field for almost 20 years, resulting that 8 innovative therapeutic cancer vaccine projects are currently under clinical investigation.

The main focus of these projects is to impact the principal cancer localizations afecting Cuban population, like …

Purification Process Development Of Protein Subunit Based Vaccine Candidates Produced Using Recombinant E. Coli Expression System (Part - Ii), Davinder Chawla, Yan-Ping Yang

Vaccine Technology III

Proteins are key components of prophylactic vaccines against infectious diseases. Protein subunit based vaccine is an attractive alternative to the traditional detoxified bacterial or inactivated viral vaccine approach due to its highly purified and well characterized product nature. Purification of protein antigens to achieve consistent product purity and quality is an integral part of the protein subunit vaccine product development process. Expression levels of the recombinant proteins in bacterial expression system may be extremely high following rapid technology advancement. The challenges and approaches used to develop purification processes for novel protein vaccine candidates expressed at g/L level will be discussed.

Influence Of Host Cell Defence During Influenza Vaccine Production In Mdck Cells, Timo Frensing, Claudius Seitz, Bjoern Heynischotto-Von-Guericke, Udo Reichl

Vaccine Technology III

For cell culture-based influenza vaccine production virus yield optimisation is of crucial importance. In particular, with the recent threat of the new H1N1 pandemic, not only seasonal vaccines but also pre-/pandemic vaccines have to be supplied in large quantities. In vivo influenza replication is limited by the immune system, but for production cell lines the impact of cellular defence mechanisms on virus yield is unknown. In influenza-infected adherent Madin-Darby canine kidney (MDCK) cells the interferon (IFN) response and subsequent induction of the antiviral state was monitored. Virus yield and host cell signalling intensity were strain-dependent. By over-expression of viral antagonists …

Final Conference Program, Barry Buckland, John Aunins, Paula Marques Alves, Kathrin Jansen

Vaccine Technology III

List of talks during the conference.

Manufacturing Flu Vaccine In Mexico: A Major Public Health And Technology Transfer Challenge, Roger Vinas

Vaccine Technology III

As Health partner of Mexican Public authorities initiative, Sanofi Pasteur is committed to build a Flu Bulk Vaccine Site, on Mexican soil, in order, for this country, to be self-sufficient for supplying seasonal vaccine and, especially,in case of a Flu Pandemic event. This presentation will give highlights on key drivers to consider while transferring this kind of Technology from Europe to Mexico: - Technology Transfer guidelines: stepwise process - Getting Permits/Authorizations - Looking for partners/Contractors: Engineering and Construction phases - Staffing ramp-up for Manufacturing (Production and Quality Control) start-up

Production Of Serotype 6-Derived Recombinant Adeno-Associated Virus In Serum-Free Suspension Cultures Of Hek 293 Cells, Érica A. Schulze

Vaccine Technology III

Recombinant adeno-associated virus (rAAV) has become a promising candidate vector for gene therapy. Anchorage-dependent cells are traditionally used to produce rAAV. However, mass production to meet demands for clinical trials requires large-scale and cost-effective manufacturing processes. The key advantages of rAAV vectors are a broader tissue tropism through the use of different serotypes and a good safety profile.

In the present work, a serotype 6-derived rAAV was produced by transfection of suspension HEK293 cells in serum-free medium using three plasmids: one encoding the GFP gene flanked by ITR sequences, the second encoding the replication and capsid genes, and a third …

Development Of Inactivated Polio Vaccine From Attenuated Sabin Strains For Clinical Studies And Technology-Transfer Purposes, Yvonne E. Thomassen, Wilfried A.M. Bakker, Janny Westdijk, Aart G. Van ‘T Oever, Nico Van Den Heuvel, Jan Hendriks, Gideon F.A. Kersten, Leo A. Van Der Pol

Vaccine Technology III

Recently, responding to WHO’s call for new polio vaccines, the development of Sabin-IPV (injectable, formalin-Inactivated Polio Vaccine, based on attenuated ‘Sabin’ polio virus strains) was initated at NVI. This activity plays an important role in the WHO polio eradication strategy. The use of Sabin instead of wild-type Salk polio strains will provide additional safety during vaccine production. Initially, the Sabin-IPV production process will be based on the scale-down model of the current, and well-established, Salk-IPV process. In parallel, process development, optimization and formulation research is being carried out to further modernize the process and reduce cost per dose. The lab-scale …

Building Process Understanding For Vaccine Manufacturing Using Data Mining, Matthew Wiener

Vaccine Technology III

The production of vaccines is a complex biological process, with long cycle times and a high level of variation in raw materials, biological growth rates, and test methods. While long-term shifts or cycles in yield are not unusual, it is important to build understanding of the causes of shifts and cycles, for greater control and predictability. Hundreds of variables are monitored for every batch of vaccine produced; however, the relationships between product quality and the many process variables are difficult to quantify. In this article, we describe how mining historical process data using random forests and partial least squares (PLS) …

Rna Based Plasmid Selection System For Antibiotic-Free Plasmid Dna Vector Production, Aaron E. Carnes, Jeremy Luke, Justin Vincent, Clague Hodgson, James Williams

Vaccine Technology III

Antibiotic resistance markers, typically kanamycin resistance (kanR), allow selective retention of plasmid DNA during bacterial fermentation and are the most commonly utilized selectable markers. However, to ensure safety, regulatory agencies recommend elimination of antibiotic resistance markers from therapeutic and vaccine plasmid DNA vectors. The presence of an antibiotic resistance gene in the plasmid backbone is considered undesirable by regulatory agencies, due to: 1) the potential transfer of antibiotic resistance to endogenous microbial flora; and 2) the potential activation and transcription of the genes from mammalian promoters after cellular incorporation into the genome. Here, we describe the development and application of …

Design Of Experiment Based Japanese Encephalitis Virus Formaldehyde Inactivation Optimisation For A Vero Cell Derived Vaccine, Michael Hughson

Vaccine Technology III

Japanese Encephalitis (JE) is a disease primarily dominant in South East Asia, caused by the Japanese Encephalitis virus (JEV). It is responsible for an estimated 50,000 cases of the disease every year, of which around 10,000 are fatal and approximately 15,000 result in long term neurological sequelae (WHO 2006). Viral inactivation is a main feature in many vaccine manufacturing processes in order not only to inactivate the product itself but also any potential adventitious agents which may have been introduced during manufacture. Chemical inactivation using formaldehyde is one of the most common methods used for inactivated viral vaccines, yet due …

New Vaccine Technologies: Promising Advances May Save More Lives, John Boslego

Vaccine Technology III

In the past 20 years, immunization has prevented nearly 20 million deaths from vaccine-preventable infections. Despite this success, poorer countries often lack access to newer and more expensive vaccines, and vaccines are not yet available for many illnesses. PATH is working to narrow the immunization gap between developed countries and developing countries by increasing the availability of existing vaccines, reducing the lag time for adoption of recently-licensed vaccines, developing technology in support of vaccines and immunization (e.g. vaccine vial monitor, Uniject, vaccine stabilization platforms) and working with partners to develop new vaccines.

Vaccine development is expensive and manufacturers often focus …

Iscomatrix™ Adjuvant Links Innate And Adaptive Immune Responses, Debbie Drane

Vaccine Technology III

The ISCOMATRIX™ adjuvant has antigen delivery and presentation properties as well as immunomodulatory capabilities which combine to provide enhanced and accelerated immune responses. The responses are broad, including a range of sub classes of antibodies as well as both CD4+ and CD8+ T cells. A range of ISCOMATRIX™ vaccines (ISCOMATRIX™ adjuvant combined with antigen) have now been tested in clinical trials and have been shown to be generally safe and well tolerated as well as immunogenic, generating both antibody and T cell responses.

The mechanisms by which ISCOMATRIX™ adjuvant facilitates its immune effects is the scope of significant study and …