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Keywords = BriLife®

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16 pages, 4219 KiB  
Article
Development and Validation of a Plaque Assay to Determine the Titer of a Recombinant Live-Attenuated Viral Vaccine for SARS-CoV-2
by Einat Toister, Lilach Cherry, Edith Lupu, Arik Monash, Eyal Dor, Lilach Levin, Meni Girshengorn, Niva Natan, Shira Chapman, Shlomo Shmaya, Eyal Epstein, Yaakov Adar, Ran Zichel, Yakir Ophir and Eran Diamant
Vaccines 2024, 12(4), 374; https://doi.org/10.3390/vaccines12040374 - 1 Apr 2024
Cited by 1 | Viewed by 4402
Abstract
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in more than seven million deaths worldwide. To reduce viral spread, the Israel Institute for Biological Research (IIBR) developed and produced a new rVSV-SARS-CoV-2-S vaccine candidate (BriLife®) [...] Read more.
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in more than seven million deaths worldwide. To reduce viral spread, the Israel Institute for Biological Research (IIBR) developed and produced a new rVSV-SARS-CoV-2-S vaccine candidate (BriLife®) based on a platform of a genetically engineered vesicular stomatitis virus (VSV) vector that expresses the spike protein of SARS-CoV-2 instead of the VSV-G protein on the virus surface. Quantifying the virus titer to evaluate vaccine potency requires a reliable validated assay that meets all the stringent pharmacopeial requirements of a bioanalytical method. Here, for the first time, we present the development and extensive validation of a quantitative plaque assay using Vero E6 cells for the determination of the concentration of the rVSV-SARS-CoV-2-S viral vector. Three different vaccine preparations with varying titers (DP_low, DP_high, and QC sample) were tested according to a strict validation protocol. The newly developed plaque assay was found to be highly specific, accurate, precise, and robust. The mean deviations from the predetermined titers for the DP_low, DP_high, and QC preparations were 0.01, 0.02, and 0.09 log10, respectively. Moreover, the mean %CV values for intra-assay precision were 18.7%, 12.0%, and 6.0%, respectively. The virus titers did not deviate from the established values between cell passages 5 and 19, and no correlation was found between titer and passage. The validation results presented herein indicate that the newly developed plaque assay can be used to determine the concentration of the BriLife® vaccine, suggesting that the current protocol is a reliable methodology for validating plaque assays for other viral vaccines. Full article
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14 pages, 2404 KiB  
Article
Development and Validation of an Innovative Analytical Approach for the Quantitation of Tris(Hydroxymethyl)Aminomethane (TRIS) in Pharmaceutical Formulations by Liquid Chromatography Tandem Mass Spectrometry
by Moran Madmon, Tamar Shamai Yamin, Shani Pitel, Chen Belay, Yaniv Segula, Einat Toister, Ariel Hindi, Lilach Cherry, Yakir Ophir, Ran Zichel, Avishai Mimran, Eran Diamant and Avi Weissberg
Molecules 2023, 28(1), 73; https://doi.org/10.3390/molecules28010073 - 22 Dec 2022
Cited by 3 | Viewed by 3831
Abstract
A novel COVID-19 vaccine (BriLife®) has been developed by the Israel Institute for Biological Research (IIBR) to prevent the spread of the SARS-CoV-2 virus throughout the population in Israel. One of the components in the vaccine formulation is tris(hydroxymethyl)aminomethane (tromethamine, TRIS), [...] Read more.
A novel COVID-19 vaccine (BriLife®) has been developed by the Israel Institute for Biological Research (IIBR) to prevent the spread of the SARS-CoV-2 virus throughout the population in Israel. One of the components in the vaccine formulation is tris(hydroxymethyl)aminomethane (tromethamine, TRIS), a buffering agent. TRIS is a commonly used excipient in various approved parenteral medicinal products, including the mRNA COVID-19 vaccines produced by Pfizer/BioNtech and Moderna. TRIS is a hydrophilic basic compound that does not contain any chromophores/fluorophores and hence cannot be retained and detected by reverse-phase liquid chromatography (RPLC)-ultraviolet (UV)/fluorescence methods. Among the few extant methods for TRIS determination, all exhibit a lack of selectivity and/or sensitivity and require laborious sample treatment. In this study, LC–mass spectrometry (MS) with its inherent selectivity and sensitivity in the multiple reaction monitoring (MRM) mode was utilized, for the first time, as an alternative method for TRIS quantitation. Extensive validation of the developed method demonstrated suitable specificity, linearity, precision, accuracy and robustness over the investigated concentration range (1.2–4.8 mg/mL). Specifically, the R2 of the standard curve was >0.999, the recovery was >92%, and the coefficient of variance (%CV) was <12% and <6% for repeatability and intermediate precision, respectively. Moreover, the method was validated in accordance with strict Good Manufacturing Practice (GMP) guidelines. The developed method provides valuable tools that pharmaceutical companies can use for TRIS quantitation in vaccines and other pharmaceutical products. Full article
(This article belongs to the Special Issue Mass Spectrometry Analysis II)
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17 pages, 4123 KiB  
Article
GIS-Based Modeling of Human Settlement Suitability for the Belt and Road Regions
by Wenjun Li, Peng Li, Zhiming Feng and Chiwei Xiao
Int. J. Environ. Res. Public Health 2022, 19(10), 6044; https://doi.org/10.3390/ijerph19106044 - 16 May 2022
Cited by 13 | Viewed by 2983
Abstract
(1) Background: Human settlements are a basic requirement for human survival and development. The natural suitability of human settlements directly affects human health and their quality of life and, to some extent, also dictates the size of the regional population and economy, as [...] Read more.
(1) Background: Human settlements are a basic requirement for human survival and development. The natural suitability of human settlements directly affects human health and their quality of life and, to some extent, also dictates the size of the regional population and economy, as well as the level of urbanization. (2) Methods: This study presents a kilometer grid-based comprehensive human settlement suitability (HSS) evaluation model (containing the relief degree of the land surface (RDLS), the temperature–humidity index (THI), the land surface water abundance index (LSWAI), and the land cover index (LCI)). (3) Results: Based on the correlations between the four factors (i.e., the normalized RDLS (NRDLS), normalized THI (NTHI), LSWAI, and LCI), the NRDLS and NTHI were determined to be the leading factors, and the LSWAI and LCI were considered to be the auxiliary factors. The auxiliary factors were used to enhance the comprehensive HSS model determined by the leading factors. Based on this logic, spatial and index models were established separately. The HSS index for the BRI regions ranged from 0.07 to 1.00. Six levels of HSS were determined—namely, unsuitable, critically unsuitable, critically suitable, generally suitable, moderately suitable, and highly suitable conditions. In particular, the human settlements suitability is dominated by critically suitable and suitable conditions that accounted for 63% of the BRI. (4) Conclusions: The evaluation results of human settlements showed that topographic and climatic conditions are important limiting factors for the suitability of human settlements. Due to the renewability and manmade adjustability of hydrological and land cover conditions, the comprehensive suitability of human settlements shows differences in different geographic spaces along the BRI. The results provide a decision-making basis for the research on the resource carrying capacity and reasonable distribution of populations in the BRI, so as to realize the sustainable development along the regions. Full article
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9 pages, 4098 KiB  
Brief Report
Neutralization of SARS-CoV-2 Variants by rVSV-ΔG-Spike-Elicited Human Sera
by Yfat Yahalom-Ronen, Noam Erez, Morly Fisher, Hadas Tamir, Boaz Politi, Hagit Achdout, Sharon Melamed, Itai Glinert, Shay Weiss, Inbar Cohen-Gihon, Ofir Israeli, Marina Izak, Michal Mandelboim, Yoseph Caraco, Noa Madar-Balakirski, Adva Mechaly, Eilat Shinar, Ran Zichel, Daniel Cohen, Adi Beth-Din, Anat Zvi, Hadar Marcus, Tomer Israely and Nir Paranadd Show full author list remove Hide full author list
Vaccines 2022, 10(2), 291; https://doi.org/10.3390/vaccines10020291 - 14 Feb 2022
Cited by 19 | Viewed by 4325
Abstract
The emergence of rapidly spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a major challenge to the ability of vaccines and therapeutic antibodies to provide immunity. These variants contain mutations of specific amino acids that might impede vaccine efficacy. BriLife [...] Read more.
The emergence of rapidly spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a major challenge to the ability of vaccines and therapeutic antibodies to provide immunity. These variants contain mutations of specific amino acids that might impede vaccine efficacy. BriLife® (rVSV-ΔG-spike) is a newly developed SARS-CoV-2 vaccine candidate currently in phase II clinical trials. It is based on a replication-competent vesicular stomatitis virus (VSV) platform. The rVSV-ΔG-spike contains several spontaneously acquired spike mutations that correspond to SARS-CoV-2 variants’ mutations. We show that human sera from BriLife® vaccinees preserve comparable neutralization titers towards alpha, gamma, and delta variants and show less than a three-fold reduction in the neutralization capacity of beta and omicron compared to the original virus. Taken together, we show that human sera from BriLife® vaccinees overall maintain a neutralizing antibody response against all tested variants. We suggest that BriLife®-acquired mutations may prove advantageous against future SARS-CoV-2 VOCs. Full article
(This article belongs to the Special Issue Effectiveness, Safety and Immunogenicity of SARS-CoV-2 Vaccines)
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24 pages, 365 KiB  
Article
Connecting into the Social Sustainability Effects of Infrastructure through China’s Digital Silk Road: Issues, Indices, and Indications
by Jean-Marc F. Blanchard and Bas Hooijmaaijers
Sustainability 2021, 13(22), 12739; https://doi.org/10.3390/su132212739 - 18 Nov 2021
Cited by 5 | Viewed by 4302
Abstract
There is a heated debate about the social-sustainability implications of infrastructure. We engage this debate by delving into China’s Digital Silk Road (DSR), an important component of China’s infrastructure-centric Belt and Road Initiative (BRI). Optimists and pessimists have offered strong views about the [...] Read more.
There is a heated debate about the social-sustainability implications of infrastructure. We engage this debate by delving into China’s Digital Silk Road (DSR), an important component of China’s infrastructure-centric Belt and Road Initiative (BRI). Optimists and pessimists have offered strong views about the DSR’s social-sustainability implications. Unfortunately, there is a dearth of analytical tools and in-depth studies which can be used to judge their competing arguments. In this article, we address these problems in two ways. First, we advance an original scheme for operationalizing social sustainability. Second, we use our framework to systematically analyze the DSR’s social-sustainability effects in Ethiopia, Malaysia, the United Arab Emirates, and Hungary. Our research indicates that much of the positive and negative commentary about the DSR’s social-sustainability implications is problematic. None of our cases show significant year-to-year changes in political or quality-of-life social-sustainability benchmarks. Indeed, our analysis indicates that analysts must pay close attention to the political and economic context to understand the social-sustainability patterns associated with DSR infrastructure. Finally, it suggests that the social-sustainability implications of DSR infrastructure are dependent on its scale and nature. These findings have ramifications for broader debates about the socioeconomic impact of infrastructure. Full article
24 pages, 2367 KiB  
Article
Temporal Patterns and Inter-Correlations among Physical and Antioxidant Attributes and Enzyme Activities of Apricot Fruit Inoculated with Monilinia laxa under Salicylic Acid and Methyl Jasmonate Treatments under Shelf-Life Conditions
by Ahmed Ezzat, Szilárd Szabó, Zoltán Szabó, Attila Hegedűs, Dorina Berényi and Imre J. Holb
J. Fungi 2021, 7(5), 341; https://doi.org/10.3390/jof7050341 - 28 Apr 2021
Cited by 29 | Viewed by 3534
Abstract
Monilinia laxa causes serious postharvest damage on apricot fruits under shelf-life storage conditions. Plant elicitors of methyl jasmonate (MeJA) and salicylic acid (SA) can reduce this damage, and their research can explain the background of the plant defense physiological processes in M. laxa [...] Read more.
Monilinia laxa causes serious postharvest damage on apricot fruits under shelf-life storage conditions. Plant elicitors of methyl jasmonate (MeJA) and salicylic acid (SA) can reduce this damage, and their research can explain the background of the plant defense physiological processes in M. laxa-infected fruits. The aims of this study were: (i) to evaluate the effect of various concentrations of MeJA and SA on brown rot incidence (BRI) and lesion diameter (LD) of apricot fruits; (ii) to measure the temporal patterns for the effect of 0.4 mmol L−1 MeJA and 2 mmol L−1 SA treatments on BRI, LD and seven fruit measures (fruit firmness (FF), lignin content (LC), total soluble phenol content (TSPC), total antioxidant capacity (TAC) and enzyme activities of PAL, POD and SOD) in treatments of M. laxa-inoculated versus (vs.) non-inoculated fruits over an eight-day shelf-life storage period; and (iii) to determine inter-correlations among the seven fruit measures for MeJA and SA treatments. Both MeJA and SA significantly reduced BRI and LD. LC, FF, TAC, TSPC, as well as SOD and PAL activities in the MeJA and SA treatments were higher than the water-treated control in most assessment days and both inoculation treatments. In both inoculation treatments, the activity of POD in the SA-treated fruits was higher than MeJA-treated and control fruits at all dates. In MeJA vs. SA and inoculated vs. non-inoculated treatments, six variable pairs (FF vs. TSPC, FF vs. TAC, TAC vs. PAL, PAL vs. POD, PAL vs. SOD, and POD vs. SOD) showed significant inter-correlation values. Principal component analyses explained 96% and 93% of the total variance for inoculated and non-inoculated treatments, respectively. In inoculated treatments, both PC1 and PC2 explained 41% of the total variance and correlated with FF, TSPC and TAC and with PAL, SOD and POD, respectively. In non-inoculated treatments, PC1 and PC2 explained 49% and 44% of the total variance and correlated with LC, PAL, POD and SOD and with FF, TSPC and TAC, respectively. It can be concluded that MeJA and SA are useful in the practice to enhance the plant defense system against brown rot by reducing fungal growth and by improving physical and antioxidant attributes (FF, LC, TAC and TSPC) and the activity of defense-related enzymes (PAL, POD and SOD) in apricot fruits during shelf-life storage conditions. Full article
(This article belongs to the Special Issue Control of Fungal Diseases in Crops)
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19 pages, 36248 KiB  
Article
An Adaptable Conceptual Model for Construction Technology Transfer: The BRI in Africa, the Case of Ethiopia
by Zahra Abdulhadi Shukra, Ying Zhou and Lingling Wang
Sustainability 2021, 13(6), 3376; https://doi.org/10.3390/su13063376 - 18 Mar 2021
Cited by 5 | Viewed by 6126
Abstract
Unlike other developmental relationships, BRI is the most promising icon in transforming the construction industry and built environment in Africa; the infrastructure developments like highways, bridges, skyscrapers, and aviation take in advanced construction technologies, methods, and skills. However, the technological capability of Chinese [...] Read more.
Unlike other developmental relationships, BRI is the most promising icon in transforming the construction industry and built environment in Africa; the infrastructure developments like highways, bridges, skyscrapers, and aviation take in advanced construction technologies, methods, and skills. However, the technological capability of Chinese construction firms is not transferred in the highest capacity to the host countries. Nevertheless, the main focus is on delivering modern railways, highways, and skyscrapers. Thus, this research aimed to propose an adaptable technology transfer model by identifying the theoretical concepts in the body of knowledge, exploring the prior technology transfer models and the best experiences. The findings indicated that the BRI inclusive countries in Africa benefit from infrastructure development with an investment amount of more than US$33 billion with potential technology spillovers, but in an unplanned, and not best suited to their conditions because of the lack of a single-country-based technology, transfer model ahead of project implementation. Using a systems thinking approach and a causal loop diagram tool, the authors created a conceptual model to guide the Africa’s construction technology transfer through BRI. The research also examined case study projects in Ethiopia to assert the new model’s practicability over the existing processes. Moreover, the university–industry linkage structures, can facilitate the process through R&D and innovation in the whole project life cycle. Full article
(This article belongs to the Special Issue Technology Innovation in Construction)
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