DNA Vaccines

2021 ◽  
Author(s):  
Jeffrey B Ulmer
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Large Scale ◽  
Dna Vaccines ◽  
Low Cost ◽  
Animal Health ◽  
Phase 3 ◽  
Efficacy Trials ◽  
Human Use

DNA vaccines were first discovered more than 30 years ago. Because DNA vaccines result in antigen production in situ (i.e., mimic a virus infection), they elicit broad-based immune responses, including antibodies and T cells. Induction of protective immunity has been established in scores of animal models of infectious and non-infectious diseases. Hundreds of human clinical trials have been conducted demonstrating safety and, in many cases, antigen-specific immune responses. Several animal health vaccines based on DNA have been approved and are in use. Many DNA vaccines are in various stages of human clinical testing, including a few in phase 3 efficacy trials and the recent Emergency Use Authorization of a COVID-19 vaccine, but to date no DNA vaccines have been fully licensed for human use. DNA vaccines are thermostable and amenable to large-scale manufacturing at relatively low cost, hence well-suited for global use, particularly in the developing world. If potency in humans could be achieved, DNA vaccines would have the potential to be a radical innovation that could disrupt the vaccine industry.

Mucosal immunization of BALB/c mice with DNA vaccines encoding the SEN1002 and SEN1395 open reading frames of Salmonella enterica serovar Enteritidis induces protective immunity

2015 ◽  
Vol 144 (2) ◽  
pp. 247-256 ◽  
Author(s):  
J. BELLO ◽  
D. SÁEZ ◽  
E. ESCALONA ◽  
P. VELOZO ◽  
C. A. SANTIVIAGO ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Dna Vaccines ◽  
Virulent Strain ◽  
Negative Control ◽  
Open Reading Frames ◽  
Secretory Iga ◽  
Salmonella Enterica Serovar Enteritidis ◽  
Humoral Immune ◽  
Limited Effectiveness

SUMMARYSalmonella Enteritidis is the main cause of foodborne salmonellosis worldwide. The limited effectiveness of current interventions against this pathogen has been the main incentive to develop new methods for the efficient control of this infection. To investigate the use of DNA vaccines against S. Enteritidis in humans, immune responses stimulated by two plasmids containing the genes designated SEN1002, located in the pathogenicity island SPI-19 and encoding a Hcp protein involved in transport mechanisms, and SEN1395, located in the genomic island ΦSE14 and encoding a protein of a new superfamily of lysozymes, were evaluated. Humoral and cellular responses following intranasal immunization of two groups of BALB/c mice with the plasmids pV1002 and pV1395 plus adjuvant were evaluated and it was observed that the IgG2a/IgG1 ratios were sixfold higher than control groups. Both plasmids stimulated specific secretory IgA production. Increased proliferation of lymphocytes and IFN-γ production were detected in both experimental groups. DNA-vaccinated mice developed protective immunity against a virulent strain of S. Enteritidis, with nearly 2 logs of protection level compared to the negative control values in the spleen. Therefore, DNA vaccines are efficient at stimulating cellular and humoral immune responses at systemic and mucosal levels.

scholarly journals An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination

2021 ◽  
Vol 118 (45) ◽  
pp. e2110817118
Author(s):  
Dengning Xia ◽  
Rui Jin ◽  
Gaurav Byagathvalli ◽  
Huan Yu ◽  
Ling Ye ◽  
...  
Keyword(s):  
Immune Responses ◽  
Large Scale ◽  
Low Cost ◽  
Electrode Array ◽  
Dna Vaccination ◽  
Intradermal Injection ◽  
Antibody Responses ◽  
Transient Effects ◽  
Electric Pulses ◽  
High Electric Field Strength

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens with pandemic potential requires safe, protective, inexpensive, and easily accessible vaccines that can be developed and manufactured rapidly at a large scale. DNA vaccines can achieve these criteria, but induction of strong immune responses has often required bulky, expensive electroporation devices. Here, we report an ultra-low-cost (<1 USD), handheld (<50 g) electroporation system utilizing a microneedle electrode array (“ePatch”) for DNA vaccination against SARS-CoV-2. The low cost and small size are achieved by combining a thumb-operated piezoelectric pulser derived from a common household stove lighter that emits microsecond, bipolar, oscillatory electric pulses and a microneedle electrode array that targets delivery of high electric field strength pulses to the skin’s epidermis. Antibody responses against SARS-CoV-2 induced by this electroporation system in mice were strong and enabled at least 10-fold dose sparing compared to conventional intramuscular or intradermal injection of the DNA vaccine. Vaccination was well tolerated with mild, transient effects on the skin. This ePatch system is easily portable, without any battery or other power source supply, offering an attractive, inexpensive approach for rapid and accessible DNA vaccination to combat COVID-19, as well as other epidemics.

scholarly journals Interfacial Manipulation via In-Situ Grown ZnSe Overlayer toward Highly Reversible Zn Metal Anodes

2021 ◽  
Author(s):  
Xianzhong Yang ◽  
Chao Li ◽  
Zhongti Sun ◽  
Shuai Yang ◽  
Zixiong Shi ◽  
...  
Keyword(s):  
Large Scale ◽  
Coulombic Efficiency ◽  
Low Cost ◽  
Chemical Vapor ◽  
Side Reactions ◽  
Water Penetration ◽  
Metal Anode ◽  
Zn Anode ◽  
Manipulation Strategy

Abstract Zn metal anode has garnered growing scientific and industrial interest owing to its appropriate redox potential, low cost and good safety. Nevertheless, the instability of Zn metal, caused by dendrite formation, hydrogen evolution and side reactions, gives rise to poor electrochemical stability and unsatisfactory cycling life, greatly hampering large-scale utilization. Herein, an in-situ grown ZnSe layer with controllable thickness is crafted over one side of commercial Zn foil via chemical vapor deposition, aiming to achieve optimized interfacial manipulation between aqueous electrolyte/Zn anode. Thus-derived ZnSe overlayer not only prevents water penetration and restricts Zn2+ two-dimensional diffusion, but also homogenizes the electric field at the interface and facilitates favorable (002) plane growth of Zn. As a result, dendrite-free and homogeneous Zn deposition is obtained; side reactions are concurrently inhibited. In consequence, a high Coulombic efficiency of 99.2% and high cyclic stability for 860 cycles at 1.0 mA cm–2 in symmetrical cells is harvested. Meanwhile, when paired with V2O5 cathode, assembled full cell achieves an outstanding initial capacity (200 mAh g–1) and elongated lifespan (a capacity retention of 84% after 1000 cycles) at 5.0 A g–1. Our highly reversible Zn anode enabled by the interfacial manipulation strategy is anticipated to satisfy the demand of industrial and commercial use.

scholarly journals In Situ EPR Characterization of a Cobalt Oxide Water Oxidation Catalyst at Neutral pH

Catalysts ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 926 ◽  
Author(s):  
Yury Kutin ◽  
Nicholas Cox ◽  
Wolfgang Lubitz ◽  
Alexander Schnegg ◽  
Olaf Rüdiger
Keyword(s):  
Cobalt Oxide ◽  
Water Oxidation ◽  
Large Scale ◽  
Low Cost ◽  
Operating Conditions ◽  
Oxidation Catalyst ◽  
O2 Evolution ◽  
Ligand Field ◽  
Neutral Ph

Here we report an in situ electron paramagnetic resonance (EPR) study of a low-cost, high-stability cobalt oxide electrodeposited material (Co-Pi) that oxidizes water at neutral pH and low over-potential, representing a promising system for future large-scale water splitting applications. Using CW X-band EPR we can follow the film formation from a Co(NO3)2 solution in phosphate buffer and quantify Co uptake into the catalytic film. As deposited, the film shows predominantly a Co(II) EPR signal, which converts into a Co(IV) signal as the electrode potential is increased. A purpose-built spectroelectrochemical cell allowed us to quantify the extent of Co(II) to Co(IV) conversion as a function of potential bias under operating conditions. Consistent with its role as an intermediate, Co(IV) is formed at potentials commensurate with electrocatalytic O2 evolution (+1.2 V, vs. SHE). The EPR resonance position of the Co(IV) species shifts to higher fields as the potential is increased above 1.2 V. Such a shift of the Co(IV) signal may be assigned to changes in the local Co structure, displaying a more distorted ligand field or more ligand radical character, suggesting it is this subset of sites that represents the catalytically ‘active’ component. The described spectroelectrochemical approach provides new information on catalyst function and reaction pathways of water oxidation.

scholarly journals Experiences with deferred grazing at the Taranaki Agricultural Research Station

1991 ◽  
pp. 79-83
Author(s):  
D.A. Mccallum ◽  
N.A. Thomson ◽  
T.G. Judd
Keyword(s):  
Agricultural Research ◽  
Low Cost ◽  
Animal Health ◽  
Research Station ◽  
Agricultural Research Station ◽  
Grazed Pasture ◽  
Dead Material ◽  
Tiller Density ◽  
Milk Solids

Deferred grazing is the practice of holding over pasture in situ that has been considered surplus to animal requirements in spring, to be grazed at a later date when a shortage of pasture occurs, usually in summer/autumn. This non-mechanical method of pasture conservation was developedandpractised from 1986-1989 at the Taranaki Agricultural Research Station as part of a low cost dairy system. At the low stocking rate (3.7 cows/ha) 13% of the farm area was conserved as deferred grazing and allowed to naturally reseed before grazing. The reseeding doubled the tiller density of perennial ryegrass, increasing pasture growth by 15 19% the following season. This, combined with the nil cost associated with conserving supplements, made this system more profitable than the traditional haysilage system. For the natural reseeding to be successful, the deferred grazed pasture should be removed from thegrazingrotationduringtheryegrassreproductive phase (mid-October to mid-November) and not grazed until after the ryegrass seed is mature (mid- January). The method developed to Wise deferred grazed pasture has been to strip graze between the morning and night milkings. Cows are offered a pasture allowance of 10 kg DM/cow/day or one, two hundred and fiftieth of the farm per day, to achieve a utilisation of around 50%. Cows graze selectively leavingaresidualofabout4000kg DM/ haofpredominantly dead material. Mowing before grazing increased utilisation, but there was no advantage in milk solids production. No benefits were observed when tall fescue or phalaris pastures were allowed to naturally reseed. Deferred grazing had no effect on grass grub or porina populations if grazed before April. No detrimental animal health effects have been measured with deferred grazing. To reduce farm operating costs and increase pasture growth, it is recommended that 10% of the farm is deferred and allowed to naturally reseed on an annual basis. Keywords deferred grazing, pasture conservation, naturalreseeding, tiller density,pasture growth, dairy production

scholarly journals Synthesis of polypeptides via bioinspired polymerization of in situ purified N-carboxyanhydrides

2019 ◽  
Vol 116 (22) ◽  
pp. 10658-10663 ◽  
Author(s):  
Ziyuan Song ◽  
Hailin Fu ◽  
Jiang Wang ◽  
Jingshu Hui ◽  
Tianrui Xue ◽  
...  
Keyword(s):  
Large Scale ◽  
Low Cost ◽  
Local Environment ◽  
Side Reactions ◽  
Scale Production ◽  
Competing Species ◽  
Natural Protein ◽  
Large Scale Production ◽  
Synthetic Polypeptides

Ribozymes synthesize proteins in a highly regulated local environment to minimize side reactions caused by various competing species. In contrast, it is challenging to prepare synthetic polypeptides from the polymerization of N-carboxyanhydrides (NCAs) in the presence of water and impurities, which induce monomer degradations and chain terminations, respectively. Inspired by natural protein synthesis, we herein report the preparation of well-defined polypeptides in the presence of competing species, by using a water/dichloromethane biphasic system with macroinitiators anchored at the interface. The impurities are extracted into the aqueous phase in situ, and the localized macroinitiators allow for NCA polymerization at a rate which outpaces water-induced side reactions. Our polymerization strategy streamlines the process from amino acids toward high molecular weight polypeptides with low dispersity by circumventing the tedious NCA purification and the demands for air-free conditions, enabling low-cost, large-scale production of polypeptides that has potential to change the paradigm of polypeptide-based biomaterials.

Versatile Metal Oxide Nanowire Devices Achieved via Controlled Doping

2007 ◽  
Vol 1018 ◽  
Author(s):  
Eric Dattoli ◽  
Qing Wan ◽  
Wei Lu
Keyword(s):  
Field Effect ◽  
Large Scale ◽  
Performance Metrics ◽  
Low Cost ◽  
Thin Film Transistor ◽  
High Electron ◽  
Glass Substrates ◽  
Sno2 Nanowires ◽  
Cost Growth

AbstractWe report on studies of field-effect transistor (FET) and transparent thin-film transistor (TFT) devices based on lightly Ta-doped SnO2 nanowires. Uniform device performance was obtained using an in situ doping method, with average field-effect mobilities exceeding 100 cm2/(V•s). Prototype fully-transparent TFT devices on glass substrates showed excellent performance metrics in terms of transconductance and on/off ratio. The combined advantages of SnO2 nanowires: namely a low cost growth process, high electron mobility, and optical transparency; make the system well suited for large-scale transparent electronics on low-temperature substrates.

scholarly journals Immunological surrogate endpoints of COVID-2019 vaccines: the evidence we have versus the evidence we need

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Pengfei Jin ◽  
Jingxin Li ◽  
Hongxing Pan ◽  
Yanfei Wu ◽  
Fengcai Zhu
Keyword(s):  
Large Scale ◽  
Current Knowledge ◽  
Surrogate Endpoints ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Efficacy Trials ◽  
Review Current

AbstractIn response to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, over 200 vaccine candidates against coronavirus disease 2019 (COVID-2019) are under development and currently moving forward at an unparalleled speed. The availability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates, which is crucial to control COVID-19 pandemic. Several phase 3 efficacy trials of COVID-19 vaccine candidates are under way, which provide opportunities for the determination of COVID-19 correlates of protection. In this paper, we review current knowledge for existence of COVID-19 correlates of protection, methods for assessment of immune correlates of protection and issues related to COVID-19 correlates of protection.

scholarly journals Fe2O3 Nanoparticles Deposited over Self-Floating Facial Sponge for Facile Interfacial Seawater Solar Desalination

Crystals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1509
Author(s):  
Yuzheng Lu ◽  
Naila Arshad ◽  
Muhammad Sultan Irshad ◽  
Iftikhar Ahmed ◽  
Shafiq Ahmad ◽  
...  
Keyword(s):  
Large Scale ◽  
High Efficiency ◽  
In Situ Polymerization ◽  
Saline Water ◽  
Low Cost ◽  
Water Yield ◽  
Fe2o3 Nanoparticles ◽  
Solar Thermal Energy ◽  
Solar Absorption

A facile approach for developing an interfacial solar evaporator by heat localization of solar-thermal energy conversion at water-air liquid composed by in-situ polymerization of Fe2O3 nanoparticles (Fe2O3@PPy) deposited over a facial sponge is proposed. The demonstrated system consists of a floating solar receiver having a vertically cross-linked microchannel for wicking up saline water. The in situ polymerized Fe2O3@PPy interfacial layer promotes diffuse reflection and its rough black surface allows Omni-directional solar absorption (94%) and facilitates efficient thermal localization at the water/air interface and offers a defect-rich surface to promote heat localization (41.9 °C) and excellent thermal management due to cellulosic content. The self-floating composite foam reveals continuous vapors generation at a rate of 1.52 kg m−2 h−1 under one 1 kW m−2 and profound evaporating efficiency (95%) without heat losses that dissipates in its surroundings. Indeed, long-term evaporation experiments reveal the negligible disparity in continuous evaporation rate (33.84 kg m−2/8.3 h) receiving two sun solar intensity, and ensures the stability of the device under intense seawater conditions synchronized with excellent salt rejection potential. More importantly, Raman spectroscopy investigation validates the orange dye rejection via Fe2O3@PPy solar evaporator. The combined advantages of high efficiency, self-floating capability, multimedia rejection, low cost, and this configuration are promising for producing large-scale solar steam generating systems appropriate for commercial clean water yield due to their scalable fabrication.

scholarly journals BNT162b2 boosted immune responses six months after heterologous or homologous ChAdOx1nCoV-19/BNT162b2 vaccination against COVID-19

2021 ◽  
Author(s):  
Georg Behrens ◽  
Joana Barros-Martins ◽  
Anne Cossmann ◽  
Gema Morillas Ramos ◽  
Metodi Stankov ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Large Scale ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Immune Protection ◽  
Cell Immunity ◽  
The Impact ◽  
As Effects

Abstract Reports suggest that COVID-19 vaccine effectiveness is decreasing, either due to waning immune protection, emergence of new variants of concern, or both. Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) appeared to be superior in inducing protective immunity, and large scale second booster vaccination is ongoing. However, data comparing declining immunity after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. We longitudinally monitored immunity in ChAd/ChAd (n=41) and ChAd/BNT (n=88) vaccinated individuals and assessed the impact of a second booster with BNT in both groups. The second booster greatly augmented waning anti-spike IgG but only moderately increased spike-specific CD4+ and CD8+ T cells in both groups to cell frequencies already present after the boost. More importantly, the second booster efficiently restored neutralizing antibody responses against Alpha, Beta, Gamma, and Delta, but neutralizing activity against B.1.1.529 (Omicron) stayed severely impaired. Our data suggest that inferior SARS-CoV-2 specific immune responses after homologous ChAd/ChAd vaccination can be cured by a heterologous BNT vaccination. However, prior heterologous ChAd/BNT vaccination provides no additional benefit for spike-specific T cell immunity or neutralizing Omicron after the second boost.

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