Biomedical Engineering and Bioengineering Commons^™

Process Scale-Up And Optimization For Production Of High Efficacy Oral Rabies Vaccine, Amine Kamen, Chun Fang Shen, Stephane Lanthier, Danielle Jacob, Johnny Montes, Andrew Beresford

Vaccine Technology III

Rabies is an important causative agent of disease resulting in an acute infection of the nervous system and death of the individual. Rabies remains an important public health program in developing countries, and the indigenous threat of rabies continues in developed countries because of wildlife reservoirs. Globally, there are about 55,000 fatal human cases of rabies each year [WHO, 2007]. Control of rabies in wildlife remains an important challenge for government offices.

There are numbers of rabies vaccines commercially available for controls of wildlife rabies. However, these vaccines currently distributed to wildlife do not effectively immunize all at-risk species, especially …

Ultra-Scale Down Studies Of Human Cell Bioprocessing For A Prostate Cancer Vaccine Therapy - The Impact Of Capillary Shear, Juan Pablo Acosta Martinez, Katherine Lawrence, Carol Chu Mike Hoare, Stephen Ward

Vaccine Technology III

The scale-up and manufacturing of therapies based on intact whole cells presents a major challenge for development scientists and engineers due to the stress-reactive nature of these cells. The administrated cells may be characterized in terms of their membrane integrity and their surface markers and eventually their biopotency. The challenge is to process the cells at various scales and in a way which maintains these cell properties. Also during formulation the presence of cytokines produced by cells prior to their inactivation is a critical factor. This poster presents an approach to allow the rapid characterization of human cell lines in …

Cim Technology: Enabeling Economic Vaccine Purification, Matjaz Peterka, Franci Smrekar, Tony Brazzale, Marko Banjac, Petra Kramberger, Milos Barut, Ales Podgornik, Ales Strancar

Vaccine Technology III

Vaccines are diverse and complex biological molecules, complexes and particles. Different production technologies are used for vaccines manufacturing and every production process require somekind of vaccine purification. Purification of vaccines is technically challenging and was traditionally inefficient and partially neglected due to different economical and technical reasons. Density gradient ultracentrifugation, introduced in1960s is still a major purification step for many vaccines present on the market. As a complementary techniques, cross flow filtration and chromatography has been used. Conventional chromatography supports designed for protein purification have relatively small pore sizes with restricted access for large molecules and viruses. In addition mass …

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 …

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) …

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.

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 …

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 …

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 …

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 …

Poly-Methyl Vinyl Ether-Co-Maleic Anhydride Nanoparticles As Antigen Delivery And Activating Systems, Carlos Gamazo, Ibai Tamayo, Ana I. Camacho

Vaccine Technology III

The incorporation of antigens into poly-methyl vinyl ether-co-maleic anhydride nanoparticles (NP) has demonstrated to enhance the immune responses in terms of a potent Th1-adjuvant capacity. This fact may be explained by the implemented possibilities that NP render to the antigen: controlled release from the vehicle and chemotaxis for APC recruitment. Besides, after oral administration, it was reported that the bioadhesive nature of the polymer enhanced the interaction of the particulate-adjuvant to the gut mucosa. Moreover, these NP allow the adhesion of antigens and ligands to its outer shell, creating high antigen density surfaces that increase the possibilities of antigen recognition …

Vaccine Stabilization – Research, Commercialization, And Impact, Ray Cummings, Debra Kristensen, Dexiang Chen, Michel Zaffran

Vaccine Technology III

Improving the stability of vaccines and removing vaccines from refrigerated storage for all or part of their shelf life have been proposed as strategies to help ensure vaccine effectiveness and to mitigate cold chain storage capacity constraints and escalating costs associated with the introduction of new vaccines into developing countries. Over the last six years, PATH has conducted research on stabilization of measles, Haemophilus influenzae type b (Hib), hepatitis B, enterotoxgenic Escherichia coli, conjugate meningococcal A, and pentavalent (Diphtheria-Tetanus-Pertussis-hepatitis B-Hib) vaccines in collaboration with 22 technical partners and 10 vaccine development groups. Results will be shared and include marked improvement …

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

Vaccine Technology III

List of talks during the conference.

The Rho Pathway Mediates Transition To An Alveolar Type I Cell Phenotype During Static Stretch Of Alveolar Type Ii Cells, Cherie D. Foster, Linda S. Varghese, Linda W. Gonzales, Susan S. Margulies, Susan H. Guttentag

Departmental Papers (BE)

Stretch is an essential mechanism for lung growth and development. Animal models in which fetal lungs have been chronically over or underdistended demonstrate a disrupted mix of type II and type I cells, with static overdistention typically promoting a type I cell phenotype. The Rho GTPase family, key regulators of cytoskeletal signaling, are known to mediate cellular differentiation in response to stretch in other organs. Using a well-described model of alveolar epithelial cell differentiation and a validated stretch device, we investigated the effects of supraphysiologic stretch on human fetal lung alveolar epithelial cell phenotype. Static stretch applied to epithelial cells …

Development Towards A Protocol To Test For The Creation Of A “Diabetic” Environment In A Blood Vessel Mimic, Kaitlyn Kirk, Development Towards A Protocol To Test For The Creation Of A “Diabetic” Environment In A Blood Vessel Mimic

Biomedical Engineering

Diabetes mellitus affects a huge proportion of people; about 6% of the population in the US had diabetes in 2007 (16). Diabetes promotes dyslipidemia, an imbalance in the circulating levels of lipids and lipoproteins, and diabetes is one of the leading risk factors for coronary artery and peripheral vascular diseases (11, 51, 52). There are two types of diabetes; type 1 diabetes accounts for about 10% of diagnosed cases and type 2 accounts for about 90% (11). Diabetic patients react differently to stents and there is a great need to enhance the treatment. The goal of this project was, and …

Effect Of Simulated Visual Impairment On Nighttime Driving Performance, Joanne Wood, Alex Chaparro, Trent Carberry, Byoung Sun Chu

Publications

Purpose. This study investigated the effects of simulated visual impairment on nighttime driving performance and pedestrian recognition under real-road conditions.

Methods. Closed road nighttime driving performance was measured for 20 young visually normal participants (M = 27.5 +- 6.1 years) under three visual conditions: normal vision, simulated cataracts, and refractive blur that were incorporated in modified goggles. The visual acuity levels for the cataract and blur conditions were matched for each participant. Driving measures included sign recognition, avoidance of low contrast road hazards, time to complete the course, and lane keeping. Pedestrian recognition was measured for pedestrians wearing either black …

The Gel Documentation System: A Cornerstone To The Implementation Of The Introduction To Biotechnology And Introduction To Bioinformatics Cross-Disciplinary Course Series, Marcy Kelly, Gregory Lampard, Constance Knapp

Cornerstone 3 Reports : Interdisciplinary Informatics

No abstract provided.

Cell-Mediated Elastic Matrix Regeneration Toward Regression Of Abdominal Aortic Aneurysms, Carmen Gacchina

All Dissertations

Abdominal aortic aneurysms (AAAs) are typically fusiform (symmetric) dilations of the aortic wall most commonly arising below the renal arteries. The progression is typically associated with an activated smooth muscle cell (SMC) phenotype, diminished density of mature medial elastic fibers, and an elevated presence of matrix-degrading enzymes (e.g., matrix-metalloproteases; MMPs), which may ultimately lead to vessel rupture. Currently, no surgical or non-surgical methods are available to regress AAAs via regeneration of new elastin matrices to regain normal vessel contour, particularly due to the inherently poor elastin synthesis by adult vascular cells and absence of methods to stimulate the same. Previously, …

Influence Of Morphology And Processing On Xps Characterisation Of Sro-Ca-Zno-Sio2 Glass, F. R. Laffir, A. W. Wren, Mark R. Towler

Chemical and Biochemical Engineering Faculty Research & Creative Works

A study was conducted to demonstrate the influence of morphology and processing on X-ray photoelectron spectroscopic (XPS) characterization SrO-Ca-ZnO-SiO₂ glass. The glass formulation being investigated was originally synthesized for developing a novel glass polyalkenoate cement (GPC). High resolution photoelectron spectra of Zn 2p, Ca 2p, Sr 3d, Si 2p, O 1s, and C 1s were recorded for the different forms of glass. It was observed that there was preferential enrichment of Zn²⁺ with an increase in the proportion of NBO for the investigated BT101 glass. The relative atomic concentration of Zn in BT101 glass was high and resulted …

Dielectrophoretic Separation Of Mouse Melanoma Clones, Ahmet C. Sabuncu, Jie A. Liu, Stephen J. Beebe, Ali Beskok

Bioelectrics Publications

Dielectrophoresis (DEP) is employed to differentiate clones of mouse melanoma B16F10 cells. Five clones were tested on microelectrodes. At a specific excitation frequency, clone 1 showed a different DEP response than the other four. Growth rate, melanin content, recovery from cryopreservation, and in vitro invasive studies were performed. Clone 1 is shown to have significantly different melanin content and recovery rate from cryopreservation. This paper reports the ability of DEP to differentiate between two malignant cells of the same origin. Different DEP responses of the two clones could be linked to their melanin content.