COVID-19 Neutralizing Antibody Surveillance Testing for Fully Vaccinated Individuals During Delta Variant Spread

We recently performed 568 rapid neutralizing antibody (NAb) tests on 164 fully vaccinated individuals who received either Moderna or Pfizer COVID-19 vaccine regimens over 7 weeks. The NAb levels against the wild type (WA1/2020), Delta, and Kappa variants were measured and compared. Depending on each individual's medical condition and vaccination status, the NAb levels for most of the fully vaccinated people decreased within 2-6 months, while a small number of individuals either generated non-detectable amount of NAbs after full vaccination (e.g., immunocompromised), or had high NAb levels lasting beyond 6 months. Since the NAb levels vary significantly among different individuals and decrease over time, the deployment of a low-cost rapid test to monitor NAb levels against both the wild type and emerging variants among fully vaccinated individuals can play a very crucial role to control the current pandemic. Our study provides an example of using such a rapid NAb test to fill this currently unmet medical need.

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SARS-CoV-2 RBD219-N1C1: A Yeast-Expressed SARS-CoV-2 Recombinant Receptor-Binding Domain Candidate Vaccine Stimulates Virus Neutralizing Antibodies and T-cell Immunity in Mice

10.1101/2020.11.04.367359 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jeroen Pollet ◽

Wen-Hsiang Chen ◽

Leroy Versteeg ◽

Brian Keegan ◽

Bin Zhan ◽

...

Keyword(s):

Recombinant Protein ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Low Cost ◽

Neutralizing Antibody ◽

Binding Domain ◽

Receptor Binding Domain ◽

Wild Type ◽

Cell Immunity

AbstractThere is an urgent need for an accessible and low-cost COVID-19 vaccine suitable for low- and middle-income countries. Here we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast (Pichia pastoris), as a suitable vaccine candidate against COVID-19. After introducing two modifications into the wild-type RBD gene to reduce yeast-derived hyperglycosylation and improve stability during protein expression, we show that the recombinant protein, RBD219-N1C1, is equivalent to the wild-type RBD recombinant protein (RBD219-WT) in an in vitro ACE-2 binding assay. Immunogenicity studies of RBD219-N1C1 and RBD219-WT proteins formulated with Alhydrogel® were conducted in mice, and, after two doses, both the RBD219-WT and RBD219-N1C1 vaccines induced high levels of binding IgG antibodies. Using a SARS-CoV-2 pseudovirus, we further showed that sera obtained after a two-dose immunization schedule of the vaccines were sufficient to elicit strong neutralizing antibody titers in the 1:1,000 to 1:10,000 range, for both antigens tested. The vaccines induced IFN-γ, IL-6, and IL-10 secretion, among other cytokines. Overall, these data suggest that the RBD219-N1C1 recombinant protein, produced in yeast, is suitable for further evaluation as a human COVID-19 vaccine, in particular, in an Alhydrogel® containing formulation and possibly in combination with other immunostimulants.

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Triticum aestivum Assay - A Useful Tool for Environmental Monitoring and Toxicity Assessment

Notulae Botanicae Horti Agrobotanici Cluj-Napoca ◽

10.15835/nbha47411349 ◽

2019 ◽

Vol 47 (4) ◽

pp. 1005-1018

Author(s):

Alexandra JITĂREANU ◽

Ioana-Cezara CABA ◽

Adriana TRIFAN ◽

Silvica PĂDUREANU ◽

Luminița AGOROAEI

Keyword(s):

Triticum Aestivum ◽

Higher Plants ◽

Low Cost ◽

Environmental Pollutants ◽

Rapid Test ◽

Toxicity Assessment ◽

Pollution Monitoring ◽

Present Review ◽

Digital Object Identifier ◽

Biological Assays

The present review summarizes the literature data regarding the application of Triticum aestivum assay as an alternative method for toxicity assessment of environmental pollutants or potential therapeutic agents. Plant bioassays present several advantages among other biological assays (simplicity, low cost, rapid test activation, a wide array of assessment endpoints). They present a good correlation with animal and human cells models, and are a reliable tool for genotoxicity assessment. Furthermore, in the context of toxicology guidelines that promote the substitution of assays using animal models with other bioassays, genotoxicity assays using higher plants models have gained in popularity. The present review focuses on three major aspects regarding Triticum aestivum assay - its utility in environmental pollution monitoring, its application in genotoxicity assessment studies, and its application in phytotoxicity evaluation of nanomaterials. ********* In press - Online First. Article has been peer reviewed, accepted for publication and published online without pagination. It will receive pagination when the issue will be ready for publishing as a complete number (Volume 47, Issue 4, 2019). The article is searchable and citable by Digital Object Identifier (DOI). DOI link will become active after the article will be included in the complete issue. *********

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Insights into neutralizing antibody responses in individuals exposed to SARS-CoV-2 in Chile

Science Advances ◽

10.1126/sciadv.abe6855 ◽

2021 ◽

Vol 7 (7) ◽

pp. eabe6855 ◽

Cited By ~ 2

Author(s):

Carolina Beltrán-Pavez ◽

Sebastián Riquelme-Barrios ◽

Aarón Oyarzún-Arrau ◽

Aracelly Gaete-Argel ◽

Roxana González-Stegmaier ◽

...

Keyword(s):

General Population ◽

Local Level ◽

Neutralizing Antibody ◽

Host Immunity ◽

Antibody Responses ◽

Wild Type ◽

Neutralization Activity ◽

Future Studies

Chile has one of the worst numbers worldwide in terms of SARS-CoV-2 positive cases and COVID-19–related deaths per million inhabitants; thus, characterization of neutralizing antibody (NAb) responses in the general population is critical to understanding of immunity at the local level. Given our inability to perform massive classical neutralization assays due to the scarce availability of BSL-3 facilities in the country, we developed and fully characterized an HIV-based SARS-CoV-2 pseudotype, which was used in a 96-well plate format to investigate NAb responses in samples from individuals exposed to SARS-CoV-2 or treated with convalescent plasma. We also identified samples with decreased or enhanced neutralization activity against the D614G spike variant compared with the wild type, indicating the relevance of this variant in host immunity. The data presented here represent the first insights into NAb responses in individuals from Chile, serving as a guide for future studies in the country.

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A20 DIAGNOSTIC ACCURACY OF A LOW COST, WIDELY AVAILABLE TEST STRIP FOR PREDICTING A POSITIVE FECAL CALPROTECTIN TEST

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.019 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 210-212

Author(s):

R Trasolini ◽

S Wong ◽

B Salh

Keyword(s):

Sample Size ◽

Likelihood Ratio ◽

Gold Standard ◽

Low Cost ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Rapid Test ◽

Test Strip ◽

Fecal Calprotectin ◽

Type I

Abstract Background Fecal calprotectin is a non-invasive test of colonic inflammation used for monitoring inflammatory bowel disease activity and for risk stratifying non-specific colonic symptoms. Calprotectin is a leukocyte specific enzyme. A similar test, leukocyte esterase is used to detect leukocytes in urine and is widely available as a low-cost point-of-care test strip. We hypothesize that an unmodified version of the urine test strip would be highly accurate in predicting a positive fecal calprotectin test in a real world sample of patients. Aims To explore a low cost, rapid alternative to the fecal calprotectin test Methods All inpatient and outpatient stool samples tested for calprotectin by the Vancouver General Hospital laboratory from February 2020 to November 2020 were included prospectively. Samples were simultaneously tested for fecal leukocyte esterase using an unmodified Roche Cobas Chemstrip urinalysis test strip by central lab personnel. An identical aliquot was sent to LifeLabs for calprotectin as per standard protocol. All samples were suspended in buffer using established laboratory protocols prior to testing. Fecal leukocyte esterase results were reported as 0–4+ based on visual interpretation, calprotectin results were reported as mcg/g of stool. REB review and approval was obtained prior to data collection. Sensitivity, Specificity and AUROC were calculated using Microsoft Excel and JROCFIT. Results 26 samples were collected. Using a fecal calprotectin greater than 120 mcg/g as a gold standard an AUROC of 0.89 (SE= .06) was calculated. A leukocyte esterase reading of 2+ or greater had the best test characteristics based on ROC curve analysis. Using this cutoff, 21/26 samples were concordant, giving an accuracy of 80.8%, sensitivity of 90.9% and specificity of 73.3%. Positive likelihood ratio was 8.07 and negative likelihood ratio was 0.29. Assuming an AUROC of 0.8, the sample size N=26 is 90% powered (β=0.9) to predict the true AUROC within 0.1 with a type I error rate of .05 (α<.05). Conclusions This study suggests application of a prepared stool sample to a urinalysis test strip gives a result highly predictive of a positive fecal calprotectin test. Further results are being collected prospectively to improve the robustness of these preliminary data. Secondary outcomes including comparison to endoscopy and biopsy results where available are planned if an adequate sample size can be accrued. Future studies justifying independent clinical use of leukocyte esterase would require a common gold standard comparator such as endoscopy. Fecal calprotectin testing is not universally insured and is not available as a rapid test strip. Use of fecal leukocyte esterase may reduce costs and shorten time to results if proven to be independently reliable. Funding Agencies None

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Modifications of Seizure Susceptibility inDrosophila

Journal of Neurophysiology ◽

10.1152/jn.2000.83.2.998 ◽

2000 ◽

Vol 83 (2) ◽

pp. 998-1009 ◽

Cited By ~ 75

Author(s):

Daniel Kuebler ◽

Mark A. Tanouye

Keyword(s):

Idiopathic Epilepsy ◽

Seizure Susceptibility ◽

Wild Type ◽

Physiological Basis ◽

Seizure Disorders ◽

Spontaneous Seizures ◽

Wide Range ◽

Symptomatic Seizures ◽

Type Strains ◽

Over Time

In a given population, certain individuals are much more likely to have seizures than others. This increase in seizure susceptibility can lead to spontaneous seizures, such as seen in idiopathic epilepsy, or to symptomatic seizures that occur after insults to the nervous system. Despite the frequency of these seizure disorders in the human population, the genetic and physiological basis for these defects remains unclear. The present study makes use of Drosophila as a potentially powerful model for understanding seizure susceptibility in humans. In addition to the genetic and molecular advantages of using Drosophila, it has been found that seizures in Drosophila share much in common with seizures seen in humans. However, the most powerful aspect of this model lies in the ability to accurately measure seizure susceptibility across genotypes and over time. In the current study seizure susceptibility was quantified in a variety of mutant and wild-type strains, and it was found that genetic mutations can modulate susceptibility over an extremely wide range. This genetic modulation of seizure susceptibility apparently occurs without affecting the threshold of individual neurons. Seizure susceptibility also varied depending on the experience of the fly, decreasing immediately after a seizure and then gradually increasing over time. A novel phenomenon was also identified in which seizures are suppressed after certain high-intensity stimuli. These results demonstrate the utility of Drosophila as a model system for studying human seizure disorders and provide insights into the possible mechanisms by which seizure susceptibility is modified.

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Structural Studies of Chikungunya Virus-Like Particles Complexed with Human Antibodies: Neutralization and Cell-to-Cell Transmission

Journal of Virology ◽

10.1128/jvi.02364-15 ◽

2015 ◽

Vol 90 (3) ◽

pp. 1169-1177 ◽

Cited By ~ 14

Author(s):

Jason Porta ◽

Vidya Mangala Prasad ◽

Cheng-I Wang ◽

Wataru Akahata ◽

Lisa F. P. Ng ◽

...

Keyword(s):

Chikungunya Virus ◽

Neutralizing Antibody ◽

Mutant Virus ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Virus Like Particles ◽

Fab Fragments ◽

Cell Transmission ◽

Viral Surface

ABSTRACTChikungunya virus is a positive-stranded RNA alphavirus. Structures of chikungunya virus-like particles in complex with strongly neutralizing antibody Fab fragments (8B10 and 5F10) were determined using cryo-electron microscopy and X-ray crystallography. By fitting the crystallographically determined structures of these Fab fragments into the cryo-electron density maps, we show that Fab fragments of antibody 8B10 extend radially from the viral surface and block receptor binding on the E2 glycoprotein. In contrast, Fab fragments of antibody 5F10 bind the tip of the E2 B domain and lie tangentially on the viral surface. Fab 5F10 fixes the B domain rigidly to the surface of the virus, blocking exposure of the fusion loop on glycoprotein E1 and therefore preventing the virus from becoming fusogenic. Although Fab 5F10 can neutralize the wild-type virus, it can also bind to a mutant virus without inhibiting fusion or attachment. Although the mutant virus is no longer able to propagate by extracellular budding, it can, however, enter the next cell by traveling through junctional complexes without being intercepted by a neutralizing antibody to the wild-type virus, thus clarifying how cell-to-cell transmission can occur.IMPORTANCEAlphaviral infections are transmitted mainly by mosquitoes. Chikungunya virus (CHIKV), which belongs to theAlphavirusgenus, has a wide distribution in the Old World that has expanded in recent years into the Americas. There are currently no vaccines or drugs against alphaviral infections. Therefore, a better understanding of CHIKV and its associated neutralizing antibodies will aid in the development of effective treatments.

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Antimicrobial Packaging

International Journal of Research in Business and Social Science (2147-4478) ◽

10.20525/ijrbs.v10i4.1251 ◽

2021 ◽

Vol 10 (4) ◽

pp. 479-484

Author(s):

Diana Merchan ◽

Mercy Agila ◽

Marina Arteaga ◽

Monica Criollo

Keyword(s):

Food Quality ◽

Food Industry ◽

Low Cost ◽

Antimicrobial Properties ◽

Renewable Sources ◽

Antimicrobial Packaging ◽

Bibliographic Analysis ◽

Antimicrobial Films ◽

Microbial Agents ◽

Over Time

Food Codex requires safe products and packaging is an important factor to comply with this consumer right, so developing packaging with antimicrobial properties that protect the product by eliminating or inhibiting bacteria or pathogens that cause damage to health is important in the food industry. The objective of this work was to perform a bibliographic analysis of some additives that generate antimicrobial properties in packaging by reviewing some studies that have developed antimicrobial films or also called smart films. Microbial agents have become an important factor in maintaining food quality over time. Biopolymers are an excellent alternative due to their availability, low cost, biodegradability and their origin are from renewable sources.

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Evolution of protection after maternal immunization for respiratory syncytial virus in cotton rats

10.1101/2021.07.30.454440 ◽

2021 ◽

Author(s):

Jorge C.G. Blanco ◽

Lori McGinnes-Cullen ◽

Arash Kamali ◽

Fatoumata Sylla ◽

Marina Boukhavalova ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Neutralizing Antibody ◽

Wild Type ◽

Cotton Rat ◽

Before And After ◽

Boost Immunization ◽

Cotton Rats ◽

Antibody Titers ◽

Syncytial Virus ◽

Efficient Transfer

Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life. In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge (Blanco, et al Journal of Virology 93: e00914-19, https://doi.org/10.1128/JVI.00914-19). Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization. We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth. However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age. This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy. The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.

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Supplier management by distributing orders among new and existing suppliers: the methodology and its application to a fast fashion company

Journal of Fashion Marketing and Management ◽

10.1108/jfmm-04-2021-0080 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Betul Acar Alagoz ◽

Murat Caner Testik ◽

Derya Dinler

Keyword(s):

Performance Evaluation ◽

Business Processes ◽

Low Cost ◽

Moving Average ◽

Holistic Approach ◽

Supplier Management ◽

Business Environment ◽

Content Type ◽

A Company ◽

Over Time

PurposeThis study aims to create a reliable, collaborative and sustainable business environment with suppliers of a company for providing high-quality and low-cost products on time. A supplier management system that sustains existing suppliers by sharing work based on systematic performance evaluation while developing the supplier base with potential suppliers is proposed.Design/methodology/approachBuilt on quantitative approaches, supplier management functions are integrated in the designed system. A quantitative strengths, weaknesses, opportunities and threats (SWOT) analysis is adapted for evaluating potential suppliers. A multi-objective integer linear programming (ILP) model is developed for the distribution of orders among selected potential and existing suppliers. A performance evaluation scheme based on an exponentially weighted moving average (EWMA) is proposed to evaluate and monitor suppliers' performance over time.FindingsProposed system develops a supplier base by methodically selecting and approving new suppliers, and a sustainable relationship with both new and existing suppliers is established based on performance over time. Decisions on retaining or removing suppliers from the base are objectively made by quantitative evaluations. Orders are fairly distributed among suppliers under the constraints imposed by the management. Dependence on a certain set of suppliers and its associated risks are reduced while agility in offering goods is enabled.Originality/valueBusiness processes for selecting new suppliers, distributing orders among all suppliers, evaluating and monitoring performance over time are quantitatively integrated to add value in operational decision-making. The proposed system is original in the holistic approach for managing and sustaining multiple suppliers of a company based on performance.

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Tracking self-reported symptoms and medical conditions on social media during the COVID-19 pandemic (Preprint)

10.2196/preprints.29413 ◽

2021 ◽

Author(s):

Qinglan Ding ◽

Daisy Massey ◽

Chenxi Huang ◽

Connor Grady ◽

Yuan Lu ◽

...

Keyword(s):

Mental Health ◽

Infectious Disease ◽

Social Media ◽

Positive Predictive Value ◽

Medical Condition ◽

Medical Conditions ◽

Health Related ◽

The U.S ◽

Over Time

BACKGROUND Harnessing health-related data posted on social media in real-time has the potential to offer insights into how the pandemic impacts the mental health and general well-being of individuals and populations over time. OBJECTIVE The aim of this study was to obtain information on symptoms and medical conditions self-reported by non-Twitter social media users during the coronavirus disease 2019 (COVID-19) pandemic, and to determine how discussion of these symptoms and medical conditions on social media changed over time. METHODS We used natural language processing (NLP) algorithms to identify symptom and medical condition topics being discussed on social media between June 14 and December 13, 2020. The sample social media posts were geotagged by NetBase, a third-party data provider. We calculated the positive predictive value and sensitivity to validate the classification of the posts. We also assessed the frequency of different health-related discussions on social media over time during the study period, and compared the changes in the frequency of each symptom/medical condition discussion to the fluctuation of U.S. daily new COVID-19 cases during the study period. Additionally, we compared the trends of the 5 most commonly mentioned symptoms and medical conditions from June 14 to August 31 (when the U.S. passed 6 million COVID-19 cases) to the trends observed from September 1 to December 13, 2020. RESULTS Within a total of 9,807,813 posts (nearly 70% were sourced from the U.S.), we identified discussion of 120 symptom topics and 1,542 medical condition topics. Our classification of the health-related posts had a positive predictive value of over 80% and an average classification rate of 92% sensitivity. The 5 most commonly mentioned symptoms on social media during the study period were: anxiety (in 201,303 posts or 12.2% of the total posts mentioning symptoms), generalized pain (189,673, 11.5%), weight loss (95,793, 5.8%), fatigue (91,252, 5.5%), and coughing (86,235, 5.2%). The 5 most discussed medical conditions were: COVID-19 (in 5,420,276 posts or 66.4% of the total posts mentioning medical conditions), unspecified infectious disease (469,356, 5.8%), influenza (270,166, 3.3%), unspecified disorders of the central nervous system (253,407, 3.1%), and depression (151,752, 1.9%). The changes in the frequency of 2 medical conditions, COVID-19 and unspecified infectious disease, were similar to the fluctuation of daily new confirmed cases of COVID-19 in the U.S. CONCLUSIONS COVID-19 and symptoms of anxiety were the two most commonly discussed health-related topics on social media from June 14 to December 13, 2020. Real-time monitoring of social media posts on symptoms and medical conditions may help assess the population's mental health status and enhance public health surveillance for infectious disease.

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