1,318 research outputs found
Manufacturing of Non-Egg Based Influenza Vaccine
Influenza is an annual health hazard with only about one-third of people in the United States receiving vaccinations for this pathogen. Epidemics are estimated to affect between 5% and 15% of the global population annually. Annually, the WHO estimates epidemics to result in between 3 and 5 million severe cases which lead to between 250,000 and 500,000 deaths. In industrialized countries, most of these deaths occur among victims who are chronically ill or are 65 years of age or older. In developing countries, particularly in tropic areas where transmission occurs year round, there is a higher rate of death to infection. For example in 2002, Madagascar experienced 800 deaths in 27,000 recorded cases of influenza over a 3 month period (WHO).
Recently, international awareness, spearheaded by the World Health Organization (WHO), has been paid to influenza since the pandemic outbreak and subsequent vaccine shortage during the H1N1 outbreak. Since then the WHO has published a set of guidelines to encourage production of safer and increasingly potent influenza vaccines for a greater number of recipients each year. WHO is attempting to increase public and private sector awareness of the importance of influenza vaccination to prevent any subsequent pandemics.
Current vaccines are produced in live, embryonated chicken eggs resulting in potential allergic reactions from animal products in the vaccines. Furthermore, this process is time-consuming and labor intensive, and the live, attenuated virus is considered to be a potential health risk for populations with suppressed immune function such as children, the elderly, and those who are sick or immunocompromised. Egg shortages can cause massive vaccine shortages, especially since only two companies currently produce most of the United States\u27 influenza vaccines. We propose that virus- like particles offer a more robust and safer alternative to current vaccine manufacturing. Currently, FluBlok is a product that utilizes recombinant influenza antigens to produce a vaccine. We plan to take this strategy another step to creating replication-deficient, native conformation viruses to induce an immune response. These particles will retain all structural similarity to native virus and have been shown to produce more robust responses with smaller doses. Furthermore, these particles will carry no risk of influenza infection upon administration. Virus-like particles will become the next generation of vaccines, such as those for human papilloma virus currently manufactured, and should rectify the problems associated with egg-based production of influenza vaccines.
The proposed process is a fed-batch operation that will create about 100 million influenza vaccines during each influenza infection season from November to February, using insect cell lines and the baculovirus expression vector system (BEVS) to induce lytic formation of virus-like particles. This process will be performed in a single-use, disposable fermentation train with single-use components integrated in the purification process to take advantage of the timesaving techniques and disposable equipment. The production of influenza vaccines is time-sensitive with a limited duration of vaccine production from WHO\u27s publishing strains to product shipment. Single-use equipment will be used to allow maximization of production time and minimization of down-time in this process
Space Suit Portable Life Support System (PLSS) 2.0 Pre-Installation Acceptance (PIA) Testing
Following successful completion of the space suit Portable Life Support System (PLSS) 1.0 development and testing in 2011, the second system-level prototype, PLSS 2.0, was developed in 2012 to continue the maturation of the advanced PLSS design. This advanced PLSS is intended to reduce consumables, improve reliability and robustness, and incorporate additional sensing and functional capabilities over the current Space Shuttle/International Space Station Extravehicular Mobility Unit (EMU) PLSS. PLSS 2.0 represents the first attempt at a packaged design comprising first generation or later component prototypes and medium fidelity interfaces within a flight-like representative volume. Pre-Installation Acceptance (PIA) is carryover terminology from the Space Shuttle Program referring to the series of test sequences used to verify functionality of the EMU PLSS prior to installation into the Space Shuttle airlock for launch. As applied to the PLSS 2.0 development and testing effort, PIA testing designated the series of 27 independent test sequences devised to verify component and subsystem functionality, perform in situ instrument calibrations, generate mapping data, define set-points, evaluate control algorithms, evaluate hardware performance against advanced PLSS design requirements, and provide quantitative and qualitative feedback on evolving design requirements and performance specifications. PLSS 2.0 PIA testing was carried out in 2013 and 2014 using a variety of test configurations to perform test sequences that ranged from stand-alone component testing to system-level testing, with evaluations becoming increasingly integrated as the test series progressed. Each of the 27 test sequences was vetted independently, with verification of basic functionality required before completion. Because PLSS 2.0 design requirements were evolving concurrently with PLSS 2.0 PIA testing, the requirements were used as guidelines to assess performance during the tests; after the completion of PIA testing, test data served to improve the fidelity and maturity of design requirements as well as plans for future advanced PLSS functional testing
Evidence of blood stage efficacy with a virosomal malaria vaccine in a Phase IIa clinical trial
Background
Previous research indicates that a combination vaccine targeting different stages of the malaria life cycle is likely to provide the most effective malaria vaccine. This trial was the first to combine two existing vaccination strategies to produce a vaccine that induces immune responses to both the pre-erythrocytic and blood stages of the P. falciparum life cycle.
Methods
This was a Phase I/IIa study of a new combination malaria vaccine FFM ME-TRAP+PEV3A. PEV3A includes peptides from both the pre-erythrocytic circumsporozoite protein and the blood-stage antigen AMA-1. This study was conducted at the Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK. The participants were healthy, malaria naïve volunteers, from Oxford. The interventions were vaccination with PEV3A alone, or PEV3A+FFM ME-TRAP. The main outcome measure was protection from malaria in a sporozoite challenge model. Other outcomes included measures of parasite specific immune responses induced by either vaccine; and safety, assessed by collection of adverse event data.
Results
We observed evidence of blood stage immunity in PEV3A vaccinated volunteers, but no volunteers were completely protected from malaria. PEV3A induced high antibody titres, and antibodies bound parasites in immunofluorescence assays. Moreover, we observed boosting of the vaccine-induced immune response by sporozoite challenge. Immune responses induced by FFM ME-TRAP were unexpectedly low. The vaccines were safe, with comparable side effect profiles to previous trials. Although there was no sterile protection two major observations support an effect of the vaccine-induced response on blood stage parasites: (i) Lower rates of parasite growth were observed in volunteers vaccinated with PEV3A compared to unvaccinated controls (p = 0.012), and this was reflected in the PCR results from PEV3A vaccinated volunteers. These showed early control of parasitaemia by some volunteers in this group. One volunteer, who received PEV3A alone, was diagnosed very late, on day 20 compared to an average of 11.8 days in unvaccinated controls. (ii). Morphologically abnormal parasites were present in the blood of all (n = 24) PEV3A vaccinated volunteers, and in only 2/6 controls (p = 0.001). We describe evidence of vaccine-induced blood stage efficacy for the first time in a sporozoite challenge study
Characterization of the Pesticide Properties of Tobacco Bio-oil
Pyrolysis converts biomass such as agricultural and forestry waste into bio-oil. Our interest in the chemical analysis of bio-oil began with tobacco, which is rich in nicotine (a known pesticide). Initial inhibition assays performed with the bio-oil on the Colorado potato beetle, a pest currently resistant to all major insecticides, showed high pesticide activity as expected. Surprisingly, the nicotine-free phases of the bio-oil were also found to be highly lethal to the beetles. Thus, it was hypothesized that some of the alkaloids in plants were preserved during pyrolysis, and gave rise to the activity.
Pesticide characteristics of tobacco and coffee bio-oils have been recorded on a number of insects as well as a variety of bacteria and fungi that do not currently respond well to chemical treatment; e.g., Streptomyces Scabies (a common potato scab disease). The current focus is to isolate and identify the components responsible for the pest inhibition, and in turn fully characterize their properties as a novel source of natural pesticides. The procedure begins with a crude separation or fractionation by distillation or extraction to simplify the chemical composition. The fractions are then screened by the activity assay. Analytical separation and mass spectral detection (GC-MS and LC-MS) are then used to generate chemical fingerprints for comparative analysis against libraries of known compounds to identify the active component(s). A mixture of chemical standards is generated from these identified, potentially active, components. This mixture is tested by the activity assay, and chemicals are sequentially removed from this mixture to identify the active components and potential synergistic effects between these components. Thus, a potential pesticide originating from agriculturally-based bio-oil is identified
Experimentally Determined Heat Transfer Coefficients for Spacesuit Liquid Cooled Garments
A Human-In-The-Loop (HITL) Portable Life Support System 2.0 (PLSS 2.0) test has been conducted at NASA Johnson Space Center in the PLSS Development Laboratory from October 27, 2014 to December 19, 2014. These closed-loop tests of the PLSS 2.0 system integrated with human subjects in the Mark III Suit at 3.7 psi to 4.3 psi above ambient pressure performing treadmill exercise at various metabolic rates from standing rest to 3000 BTU/hr (880 W). The bulk of the PLSS 2.0 was at ambient pressure but effluent water vapor from the Spacesuit Water Membrane Evaporator (SWME) and the Auxiliary Membrane Evaporator (Mini-ME), and effluent carbon dioxide from the Rapid Cycle Amine (RCA) were ported to vacuum to test performance of these components in flight-like conditions. One of the objectives of this test was to determine the heat transfer coefficient (UA) of the Liquid Cooling Garment (LCG). The UA, an important factor for modeling the heat rejection of an LCG, was determined in a variety of conditions by varying inlet water temperature, flowrate, and metabolic rate. Three LCG configurations were tested: the Extravehicular Mobility Unit (EMU) LCG, the Oceaneering Space Systems (OSS) LCG, and the OSS auxiliary LCG. Other factors influencing accurate UA determination, such as overall heat balance, LCG fit, and the skin temperature measurement, will also be discussed
Experimentally Determined Overall Heat Transfer Coefficients for Spacesuit Liquid Cooled Garments
A Human-In-The-Loop (HITL) Portable Life Support System 2.0 (PLSS 2.0) test has been conducted at NASA Johnson Space Center in the PLSS Development Laboratory from October 27, 2014 to December 19, 2014. These closed-loop tests of the PLSS 2.0 system integrated with human subjects in the Mark III Suit at 3.7 psi to 4.3 psi above ambient pressure performing treadmill exercise at various metabolic rates from standing rest to 3000 BTU/hr (880 W). The bulk of the PLSS 2.0 was at ambient pressure but effluent water vapor from the Spacesuit Water Membrane Evaporator (SWME) and the Auxiliary Membrane Evaporator (Mini-ME), and effluent carbon dioxide from the Rapid Cycle Amine (RCA) were ported to vacuum to test performance of these components in flight-like conditions. One of the objectives of this test was to determine the overall heat transfer coefficient (UA) of the Liquid Cooling Garment (LCG). The UA, an important factor for modeling the heat rejection of an LCG, was determined in a variety of conditions by varying inlet water temperature, flow rate, and metabolic rate. Three LCG configurations were tested: the Extravehicular Mobility Unit (EMU) LCG, the Oceaneering Space Systems (OSS) LCG, and the OSS auxiliary LCG. Other factors influencing accurate UA determination, such as overall heat balance, LCG fit, and the skin temperature measurement, will also be discussed
Directional wetting in anisotropic inverse opals
Porous materials display interesting transport phenomena due to the restricted motion of fluids within the nano- to micro-scale voids. Here, we investigate how liquid wetting in highly ordered inverse opals is affected by anisotropy in pore geometry. We compare samples with different degrees of pore asphericity and find different wetting patterns depending on the pore shape. Highly anisotropic structures are infiltrated more easily than their isotropic counterparts. Further, the wetting of anisotropic inverse opals is directional, with liquids filling from the side more easily. This effect is supported by percolation simulations as well as direct observations of wetting using time-resolved optical microscopy
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Directional Wetting in Anisotropic Inverse Opals
Porous materials display interesting transport phenomena due to the restricted motion of fluids within the nano- to micro-scale voids. Here, we investigate how liquid wetting in highly ordered inverse opals is affected by anisotropy in pore geometry. We compare samples with different degrees of pore asphericity and find different wetting patterns depending on the pore shape. Highly anisotropic structures are infiltrated more easily than their isotropic counterparts. Further, the wetting of anisotropic inverse opals is directional, with liquids filling from the side more easily. This effect is supported by percolation simulations as well as direct observations of wetting using time-resolved optical microscopy.Chemistry and Chemical Biolog
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