Biomedical Engineering and Bioengineering Commons^™

Potent, Rapid And Cost-Effective Influenza Vaccines Made In E. Coli, Thomas Hofstaetter

Vaccine Technology III

The traditional influenza vaccine, trivalent inactivated virus (TIV) has been in use in the United States in one form or another since the 1940s. The system for production involves injecting influenza virus into embryonated hen’s eggs, harvesting the allantoic fluid containing the virus, inactivation with formalin, disruption of the virus with non-ionic detergent, zonal centrifugation to enrich for antigen and a second inactivation step. The recent appearance of the H1N1 swine virus has provided an opportunity to test the pandemic response system established over the past ten years. What we find is that the public health system seems to work …

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 …

Clinical Development Of Formulated Therapeutic And Prophylactic Dna-Based Vaccines, Alain Rolland

Vaccine Technology III

Over the recent years, plasmid DNA vaccines have reached licensure against infectious hematopoietic necrosis virus in farmed salmon (Canada), West Nile virus in horses and metastatic melanoma in dogs (United States). A number of approaches are currently evaluated in clinical trials to enhance the potency of DNA vaccines in humans, including formulation of DNA with delivery systems and adjuvants as well as administration of DNA with devices. This presentation will report on the development of TransVaxTM, a poloxamer-formulated therapeutic DNA vaccine against human cytomegalovirus (CMV) in transplant patients. A vaccine that increases CMV-specific T-cell responses could reduce CMV reactivation after …

Development Of Recombinant Protein Based Chemical Conjugate Malaria Vaccines Targeting The Pre-Erythrocytic Stage, Transmission Blocking, Or Both, David L. Narum, Nicholas Macdonald, David Jones, Ruth Ellis, Yimin Wu, Patrick E. Duffy

Vaccine Technology III

The development of a Plasmodium falciparum malaria vaccine is critical for future control and elimination programs. Recombinant protein based chemical conjugate vaccines, covering different parasite stages, are being developed due to complexity of the parasite and sub-optimal immunogenicity of recombinant malaria proteins in humans, respectively. Chemical conjugation of recombinant malaria proteins to carrier proteins improves their immunogenicity in animal studies. A transmission blocking vaccine comprised of the ookinete protein Pfs25 chemically conjugated to Pseudomonas aeruginosa ExoProtein A (EPA) is currently being developed for pilot scale cGMP production. Bulk lots of Pfs25 and EPA have already been produced and released following …

The Challenge Of Developing New Generation Vaccines For Control And Eradication Of Foot And Mouth Disease In South America, Susana Levy

Vaccine Technology III

Foot and mouth disease (FMD) is a highly infectious viral disease that affects food producing animals such as cattle, pigs and sheep. The FMD status given by the World Organization for Animal Health (OIE) has a huge financial impact on countries that have economies based on meat trade. In the past 15 years the MERCOSUR countries (Argentina, Brazil, Paraguay and Uruguay) have consolidated industrial processes to supply the region with safe and efficacious vaccines to prevent FMD in livestock. Control and eradication programs rely heavily on compulsory vaccination with multivalent whole virus inactivated vaccines. Currently, vaccines are industrially obtained by …

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 …

Establishing A Platform For Spray Drying Inhalable Vaccines In South Africa, Willem Germishuizen, L Venter, A Khosa, F Mudau, P.B. Fourie, B Pulliam, M Kabadi, A Schiermeier, D.A . Edwards

Vaccine Technology III

Mycobacterium bovis BCG is the current vaccine for tuberculosis (TB). However, BCG as it is currently administered shows highly variable efficacy in protecting adults against TB. The natural route of infection of TB is via inhalation of bacilli-containing aerosols and it is postulated that immunization by the natural route of infection may lead to a greater immunity given the fact that the lungs are the primary target of infection. By eliciting both local and systemic immune responses, it is anticipated that an inhaled form of BCG will offer greater protection against pulmonary TB.

Current commercial BCG vaccine preparations are filled …

Scale-Up Of An Intensified Process For Rad35 Adenovirus Production Using The Per.C6® Cell Substrate, Alfred Luitjens, Herman Van Herk

Vaccine Technology III

Tuberculosis is the world’s second deadliest infectious disease, with over 9 million new cases diagnosed in 2006. In collaboration with the Aeras Global Tuberculosis Vaccine Foundation, we are developing a recombinant tuberculosis adenovirus based vaccine (rAd35). Currently a series of three Phase I trials are taking place, with the first two studies indicating very promising results, safety and toleration. In November 2008 we started a Phase II study in South Africa. The manufacturing process supporting these clinical studies was developed using the PER.C6® cell substrate. With the productivity of this production process, scale-up to 10,000-liter bioreactor will be required to …

Application Of Animal-Free Recombinant Bioactive Protein Supplements To Improve The Performance Of Cell-Based Viral Vaccine Production, Kenneth Bertram, Marina Ross, Domenica Cavallaro, Larissa Chirkova, Geoffrey Francis

Vaccine Technology III

Animal cell culture for the production of viral vaccines has been performed for more than 50 years, and currently this technology is expanding rapidly to meet present and future demands of the health sector. The development and regulatory approval of continuous cell lines for manufacturing viral vaccines has brought numerous benefits to production processes. However, greater advances in the last decade have been achieved in mammalian cell production of biological therapeutics, including monoclonal antibodies, hormones, growth factors, cytokines and clotting factors. We and others have contributed to these upstream advances by improving cell culture media with the development of animal-free …

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 …

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.

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 …

Frontal Plane Humeral Elevation Effects On The Pullout Strength Of Suture Anchors Used In Rotator Cuff Repair, Peter Joshua Larson

Master's Theses

The rotator cuff offers the stabilizing forces necessary for fine arm movement. The most common injury to the rotator cuff is the partial or full thickness tear of the supraspinatus tendon, which attaches the humerus to the scapula on the superior side, due to an acute or chronic injury. These injuries account for more than 4.5 million physician visits per year. Depending on the degree of tear, arthroscopic surgery may be needed to reattach the torn tendon to the humeral head. The current preferred method of surgery involves the insertion of a suture anchor into the humeral head that ties …

Antenna Development For Radio Frequency Hyperthermia Applications, Sergio Curto

Doctoral

This thesis deals with the design steps, development and validation of an applicator for radio frequency hyperthermia cancer therapy. An applicator design to enhance targeted energy coupling is a key enabler for preferential temperature increments in tumour regions. A single-element, near-field approach requires a miniaturised solution, that addresses ergonomic needs and is tolerant to patient anatomy. The antenna war-field rriodality and the high-dielectric patient loading introduce significant analytical and computational resource challenges. The antenna input impedance has to be sufficiently insensitive to in-band resonant cletuning and the fields in the tissue can he targeted to selected areas in the patient. …

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 …

Epidermal Neural Crest Stem Cell (Epi-Ncsc)--Mediated Recovery Of Sensory Function In A Mouse Model Of Spinal Cord Injury, Yao Fei Hu, Krishnaj Gourab, Clive Wells, Oliver Clives, Brian D. Schmit, Maya Sieber-Blum

Biomedical Engineering Faculty Research and Publications

Here we show that epidermal neural crest stem cell (EPI-NCSC) transplants in the contused spinal cord caused a 24% improvement in sensory connectivity and a substantial recovery of touch perception. Furthermore we present a novel method for the ex vivo expansion of EPI-NCSC into millions of stem cells that takes advantage of the migratory ability of neural crest stem cells and is based on a new culture medium and the use of microcarriers. Functional improvement was shown by two independent methods, spinal somatosensory evoked potentials (SpSEP) and the Semmes-Weinstein touch test. Subsets of transplanted cells differentiated into myelinating oligodendrocytes. Unilateral …

Exploiting The Concept Of Hysteresis In Ankle Dysfunction And Ankle Strengthening, Akshay Narendra Pujara

Theses

The ankle joint is an important part of the body which is responsible for normal gait cycle. Dorsiflexion, plantar flexion, inversion and eversion are four types of movements controlled by the ankle joint. All these movements are controlled by the ligaments and the muscles associated with the ankle. Disorders of these ligaments and muscles leads to ankle dysfunction.

The hysteresis concept was employed to determine if there is any ankle dysfunction. A recently developed device, the Ankle Torsion Monitor (AnTm) was employed to evaluate the viscoelasticity and stiffness of the ankle joint. The greater the hysteresis loop area (HLA) the …