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 Inverse Vaccination to Silence Immunity to Myelin in Multiple Sclerosis

2010 ◽  
Vol 37 (S2) ◽  
pp. S49-S58 ◽  
Author(s):  
Lawrence Steinman
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Clinical Trials ◽  
Immune Responses ◽  
Large Scale ◽  
Adaptive Immune Response ◽  
Antibody Responses ◽  
Myelin Proteins ◽  
Adaptive Immune ◽  
Key Drivers

ABSTRACT:The adaptive immune response in multiple sclerosis is complex. We have devised large scale arrays to measure the antibody response to myelin proteins and lipids. Despite the widespread immune responses to myelin, we have devised an inverse vaccine aimed at turning off key drivers of this diverse response. Clinical trials in patients with multiple sclerosis show that it is possible to constrain antibody responses to myelin on a large scale with this approach.

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.

scholarly journals A Newcastle disease virus-vector expressing a prefusion-stabilized spike protein of SARS-CoV-2 induces protective immune responses against prototype virus and variants of concern in mice and hamsters

2021 ◽  
Author(s):  
Weina Sun ◽  
Yonghong Liu ◽  
Fatima Amanat ◽  
Irene González-Domínguez ◽  
Stephen McCroskery ◽  
...  
Keyword(s):  
Immune Responses ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Large Scale ◽  
Rapid Development ◽  
Influenza Virus Vaccine ◽  
Antibody Responses ◽  
High Yields ◽  
Prototype Virus

Abstract Rapid development of coronavirus disease 2019 (COVID-19) vaccines and expedited authorization for use and approval has been proven beneficial to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and given hope in this desperate situation. It is believed that sufficient supplies and equitable allocations of vaccines are necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here we provide evidence that the NDV vector expressing an optimized spike antigen (NDV-HXP-S), upgraded from our previous construct, is a versatile vaccine that can be used live or inactivated to induce strong antibody responses and to also cross-neutralize variants of concern. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters. It is noteworthy that vaccine lots produced by existing egg-based influenza virus vaccine manufacturers in Vietnam, Thailand and Brazil exhibited excellent immunogenicity and efficacy in hamsters, demonstrating that NDV-HXP-S vaccines can be quickly produced at large-scale to meet global demands.

scholarly journals A Newcastle disease virus-vector expressing a prefusion-stabilized spike protein of SARS-CoV-2 induces protective immune responses against prototype virus and variants of concern in mice and hamsters

2021 ◽  
Author(s):  
Weina Sun ◽  
Yonghong Liu ◽  
Fatima Amanat ◽  
Irene Gonzalez-Dominguez ◽  
Stephen McCroskery ◽  
...  
Keyword(s):  
Immune Responses ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Large Scale ◽  
Rapid Development ◽  
Influenza Virus Vaccine ◽  
Antibody Responses ◽  
High Yields ◽  
Prototype Virus

Rapid development of coronavirus disease 2019 (COVID-19) vaccines and expedited authorization for use and approval has been proven beneficial to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and given hope in this desperate situation. It is believed that sufficient supplies and equitable allocations of vaccines are necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here we provide evidence that the NDV vector expressing an optimized spike antigen (NDV-HXP-S), upgraded from our previous construct, is a versatile vaccine that can be used live or inactivated to induce strong antibody responses and to also cross-neutralize variants of concern. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters. It is noteworthy that vaccine lots produced by existing egg-based influenza virus vaccine manufacturers in Vietnam, Thailand and Brazil exhibited excellent immunogenicity and efficacy in hamsters, demonstrating that NDV-HXP-S vaccines can be quickly produced at large-scale to meet global demands.

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.

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

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

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.

An Assessment of a Low-Cost Wastewater Disposal System after Twenty-Five Years of Operation

1987 ◽  
Vol 19 (5-6) ◽  
pp. 701-710 ◽  
Author(s):  
B. L. Reidy ◽  
G. W. Samson
Keyword(s):  
Large Scale ◽  
Low Cost ◽  
Wastewater Disposal ◽  
Industrial Base ◽  
Industrial Wastewaters ◽  
The Past ◽  
Gasification Process ◽  
Appropriate Treatment ◽  
Environmentally Safe ◽  
Coal Resource

A low-cost wastewater disposal system was commissioned in 1959 to treat domestic and industrial wastewaters generated in the Latrobe River valley in the province of Gippsland, within the State of Victoria, Australia (Figure 1). The Latrobe Valley is the centre for large-scale generation of electricity and for the production of pulp and paper. In addition other industries have utilized the brown coal resource of the region e.g. gasification process and char production. Consequently, industrial wastewaters have been dominant in the disposal system for the past twenty-five years. The mixed industrial-domestic wastewaters were to be transported some eighty kilometres to be treated and disposed of by irrigation to land. Several important lessons have been learnt during twenty-five years of operating this system. Firstly the composition of the mixed waste stream has varied significantly with the passage of time and the development of the industrial base in the Valley, so that what was appropriate treatment in 1959 is not necessarily acceptable in 1985. Secondly the magnitude of adverse environmental impacts engendered by this low-cost disposal procedure was not imagined when the proposal was implemented. As a consequence, clean-up procedures which could remedy the adverse effects of twenty-five years of impact are likely to be costly. The question then may be asked - when the total costs including rehabilitation are considered, is there really a low-cost solution for environmentally safe disposal of complex wastewater streams?

scholarly journals Rapid, large-scale species discovery in hyperdiverse taxa using 1D MinION sequencing

BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Amrita Srivathsan ◽  
Emily Hartop ◽  
Jayanthi Puniamoorthy ◽  
Wan Ting Lee ◽  
Sujatha Narayanan Kutty ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Large Scale ◽  
Low Cost ◽  
Small Body ◽  
Small Subset ◽  
Similar Species ◽  
Large Species ◽  
Morphological Examination ◽  
Species Discovery ◽  
Short Period

Abstract Background More than 80% of all animal species remain unknown to science. Most of these species live in the tropics and belong to animal taxa that combine small body size with high specimen abundance and large species richness. For such clades, using morphology for species discovery is slow because large numbers of specimens must be sorted based on detailed microscopic investigations. Fortunately, species discovery could be greatly accelerated if DNA sequences could be used for sorting specimens to species. Morphological verification of such “molecular operational taxonomic units” (mOTUs) could then be based on dissection of a small subset of specimens. However, this approach requires cost-effective and low-tech DNA barcoding techniques because well-equipped, well-funded molecular laboratories are not readily available in many biodiverse countries. Results We here document how MinION sequencing can be used for large-scale species discovery in a specimen- and species-rich taxon like the hyperdiverse fly family Phoridae (Diptera). We sequenced 7059 specimens collected in a single Malaise trap in Kibale National Park, Uganda, over the short period of 8 weeks. We discovered > 650 species which exceeds the number of phorid species currently described for the entire Afrotropical region. The barcodes were obtained using an improved low-cost MinION pipeline that increased the barcoding capacity sevenfold from 500 to 3500 barcodes per flowcell. This was achieved by adopting 1D sequencing, resequencing weak amplicons on a used flowcell, and improving demultiplexing. Comparison with Illumina data revealed that the MinION barcodes were very accurate (99.99% accuracy, 0.46% Ns) and thus yielded very similar species units (match ratio 0.991). Morphological examination of 100 mOTUs also confirmed good congruence with morphology (93% of mOTUs; > 99% of specimens) and revealed that 90% of the putative species belong to the neglected, megadiverse genus Megaselia. We demonstrate for one Megaselia species how the molecular data can guide the description of a new species (Megaselia sepsioides sp. nov.). Conclusions We document that one field site in Africa can be home to an estimated 1000 species of phorids and speculate that the Afrotropical diversity could exceed 200,000 species. We furthermore conclude that low-cost MinION sequencers are very suitable for reliable, rapid, and large-scale species discovery in hyperdiverse taxa. MinION sequencing could quickly reveal the extent of the unknown diversity and is especially suitable for biodiverse countries with limited access to capital-intensive sequencing facilities.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

scholarly journals An efficient direct screening system for microorganisms that activate plant immune responses based on plant–microbe interactions using cultured plant cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mari Kurokawa ◽  
Masataka Nakano ◽  
Nobutaka Kitahata ◽  
Kazuyuki Kuchitsu ◽  
Toshiki Furuya
Keyword(s):  
Immune Responses ◽  
Plant Defense ◽  
Pseudomonas Syringae ◽  
Large Scale ◽  
Plant Cells ◽  
Defense Responses ◽  
Root Tip ◽  
General Strategy ◽  
Plant Defense Responses ◽  
Microbe Interactions

AbstractMicroorganisms that activate plant immune responses have attracted considerable attention as potential biocontrol agents in agriculture because they could reduce agrochemical use. However, conventional methods to screen for such microorganisms using whole plants and pathogens are generally laborious and time consuming. Here, we describe a general strategy using cultured plant cells to identify microorganisms that activate plant defense responses based on plant–microbe interactions. Microbial cells were incubated with tobacco BY-2 cells, followed by treatment with cryptogein, a proteinaceous elicitor of tobacco immune responses secreted by an oomycete. Cryptogein-induced production of reactive oxygen species (ROS) in BY-2 cells served as a marker to evaluate the potential of microorganisms to activate plant defense responses. Twenty-nine bacterial strains isolated from the interior of Brassica rapa var. perviridis plants were screened, and 8 strains that enhanced cryptogein-induced ROS production in BY-2 cells were selected. Following application of these strains to the root tip of Arabidopsis seedlings, two strains, Delftia sp. BR1R-2 and Arthrobacter sp. BR2S-6, were found to induce whole-plant resistance to bacterial pathogens (Pseudomonas syringae pv. tomato DC3000 and Pectobacterium carotovora subsp. carotovora NBRC 14082). Pathogen-induced expression of plant defense-related genes (PR-1, PR-5, and PDF1.2) was enhanced by the pretreatment with strain BR1R-2. This cell–cell interaction-based platform is readily applicable to large-scale screening for microorganisms that enhance plant defense responses under various environmental conditions.

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