Safety and immunogenicity of a recombinant receptor-binding domain-based protein subunit vaccine (Noora vaccine™) against COVID-19 in adults: A randomized, double-blind, placebo-controlled, Phase 1 trial.

The development of a safe and effective vaccine is essential to protect populations against coronavirus disease 2019 (COVID-19). There are several vaccine candidates under investigation with different mechanisms of action. In the present study, we have evaluated the safety and immunogenicity of a recombinant receptor-binding domain (RBD)-based protein subunit vaccine (Noora vaccine) against COVID-19 in adults. This Phase 1 trial is a randomized, double-blind, placebo-controlled study to evaluate the safety and immunogenicity of the recombinant RBD-based protein subunit vaccine (Noora vaccine) against COVID-19 in healthy adults volunteers. Eligible participants were included in this study after evaluating their health status and considering the exclusion criteria. They were then randomized into three groups and received three doses of vaccine (80 µg, 120 µg, and placebo) on Days 0, 21, and 35. Primary outcomes including solicited, unsolicited, and medically attended adverse events were recorded during this study. Secondary outcomes including the humoral and cellular immunity (including anti-RBD IgG antibody and neutralizing antibody) were measured on Days 0, 21, 28, 35, 42, and 49 by using the ELISA kit and the Virus Neutralization Test (VNT) was performed on day 49. Totally 70 cases were included in this Phase 1 trial and 60 of them completed the study. Safety assessments showed no severe adverse events. Local pain at the vaccine injection site occurred in 80% of the vaccinated volunteers. Induration and redness at the injection site were the other adverse reactions of this vaccine. There was no significant difference between the studied groups regarding adverse reactions. Anti-RBD IgG antibody and neutralizing antibody assessment showed significant seroconversion in comparison to the placebo group (80%, and 100% respectively, p < 0.001). The cellular immunity panel also showed mild to moderate induction of TH1 responses and the VNT showed 78% of seroprotection. The results of this Phase 1 trial showed acceptable safety without serious adverse events and significant seroconversions in the humoral and cellular immunity panel. The dose of 80 µg is an appropriate dose for injection in the next phases of the trial.

Safety and immunogenicity of an inactivated virus particle vaccine for SARS-CoV-2, BIV1-CovIran: findings from double-blind, randomised, placebo-controlled, phase I and II clinical trials among healthy adults.

OBJECTIVE: Assessing safety and immunogenicity of an inactivated whole virus particle vaccine. DESIGN: Single-centre, double-blind, randomised, placebo-controlled, phase I (stage I: 18-50, stage II: 51-75 years), phase II (18-75 years) clinical trials. SETTING: 29 December 2020 to 22 April 2021. PARTICIPANTS: Stage I-phase I: 56 participants; stage II-phase I: 32; phase II: 280. INTERVENTION: During stage I, participants randomly (3:3:1) received 3 µg, 5 µg vaccine or placebo in a 14-day interval. Participants in stage II received two shots of 5 µg vaccine or placebo (3:1). In phase II, participants received 5 µg vaccine or placebo (4:1) in a 28-day interval. PRIMARY AND SECONDARY OUTCOME MEASURES: Safety assessment and immunogenicity assessment via antibody response and conventional virus neutralisation test (cVNT). RESULTS: All adverse events (AEs) were mild or moderate and transient in both phase I and phase II, and no AEs of special interest were reported. The seroconversion-rate of neutralising, antireceptor binding-domain (RBD) and anti-spike-glycoprotein (anti-S) antibodies 14-days after second dose of 5 µg vaccine in stage I was 70.8% (95% CI 48.9% to 87.4%), 87.5% (95% CI 67.6% to 97.3%), 91.7% (95% CI 73.0% to 99.0%). The antibody titres increased more among 5 µg than 3 µg. The corresponding rates for 3 µg vaccine were 45.8% (95% CI 25.6% to 67.2%), 54.2% (95% CI 32.8% to 74.5%) and 70.8% (95% CI 48.9% to 87.4%), respectively. In stage II, 100% (95% CI 84.6% to 100%), 86.4% (95% CI 65.1% to 97.1%) and 86.4% (95% CI 65.1% to 97.1%) of participants seroconverted for neutralising, anti-RBD and anti-S antibodies. In phase II, the seroconversion rate of neutralising-antibody was 82.8% (95% CI 77.0% to 87.6%), anti-RBD 77.0% (95% CI 70.7% to 82.6%) and anti-S 79.9% (95% CI 73.8% to 85.1%) on day 42. In the cVNT, the sera at 1/64 times dilution would neutralise SARS-CoV-2 among 91.7%, 77.3% and 82.5% of vaccinated participants in phase I-stage I, phase I-stage II and phase II clinical trials, respectively. CONCLUSIONS: These results support further evaluation of this inactivated whole virus particle vaccine. TRIAL REGISTRATION NUMBERS: IRCT20201202049567N1 and IRCT20201202049567N2 for phase I and IRCT20201202049567N3 for phase II.

Methods to disinfect and decontaminate SARS-CoV-2: a systematic review of in vitro studies.

BACKGROUND: Cleaning is a major control component for outbreaks of infection. However, for the SARS-CoV-2 pandemic, there is limited specific guidance regarding the proper disinfection methods that should be used. METHODS: We conducted a systematic review of the literature on cleaning, disinfection or decontamination methods in the prevention of SARS-CoV-2. RESULTS: A total of 27 studies were included, reporting a variety of methods with which the effectiveness of interventions were assessed. Virus was inoculated onto different types of material including masks, nasopharyngeal swabs, serum, laboratory plates and simulated saliva, tears or nasal fluid and then interventions were applied in an attempt to eliminate the virus including chemical, ultraviolet (UV) light irradiation, and heat and humidity. At body temperature (37°C) there is evidence that the virus will not be detectable after 2 days but this can be reduced to non-detection at 30 min at 56°C, 15 min at 65°C and 2 min at 98°C. Different experimental methods testing UV light have shown that it can inactivate the virus. Light of 254-365 nm has been used, including simulated sunlight. Many chemical agents including bleach, hand sanitiser, hand wash, soap, ethanol, isopropanol, guandinium thiocynate/t-octylphenoxypolyethoxyethanol, formaldehyde, povidone-iodine, 0.05% chlorhexidine, 0.1% benzalkonium chloride, acidic electrolysed water, Clyraguard copper iodine complex and hydrogen peroxide vapour have been shown to disinfect SARS-CoV-2. CONCLUSIONS: Heating, UV light irradiation and chemicals can be used to inactivate SARS-CoV-2 but there is insufficient evidence to support one measure over others in clinical practice.

Protection of Sensitive Loads in Distribution Systems Using a BSFCL-DVR System.

In this paper, an incorporated bridge-type superconducting fault current limiter (BSFCL) and Dynamic Voltage Restorer (DVR) is presented to improve the voltage quality and limiting fault current problems in distribution systems. In order to achieve these capabilities, the BSFCL and DVR are integrated through a common DC link as a BSFCL-DVR system. The FCL and DVR ports of the BSFCL-DVR system are located in the beginning and end of the sensitive loads' feeder integrated to the point of common coupling (PCC) in the distribution system. At first, the principle operation of the BSFCL-DVR is discussed. Then, a control system for the BSFCL-DVR system is designed to enhance the voltage quality and limit the fault current. Eventually, the efficiency of the BSFCL-DVR system is verified through the PSCAD/EMTDC simulation.

Nasojugal Flap with Dermal Pennant for Reconstructive of Lower Lid Defect.

BACKGROUND: Basal cell carcinomas (BCCs) are locally invasive periocular skin cancers affecting lower eyelids more than upper eyelids. The purpose of this study was to describe techniques used for lower eyelid reconstruction after extended excision of BCC. METHODS: Eight referred patients with BCC who underwent lower eyelid reconstruction were enrolled. The tumor was surgically excised with sufficient margins by one surgeon. Defects were repaired by subdermal tunnel between lateral border of defect and insertion site of lateral cantus. RESULTS: Eight patients aged 45 to 75 years were followed up for 6 months. After follow up, adequate viability of the grafts, satisfactory functional and good cosmetic results was noticed in all patients. One patient complained of irritation at the site of surgery. No total or partial necrosis, hematoma, or infection were observed in flaps, and no additional surgery was needed. CONCLUSION: The present novel surgical procedure was useful to close full thickness defects in the lower lid to preserve the function of the lower eyelid and a good aesthetic outcome.

Effect of Ethanol on Micro-Vessels Diameter and Prevention of Thrombosis.

BACKGROUND: Microvascular surgery is one of the most important parts of reconstructive surgery. In the present study, the effect of ethanol on microvascular diameter and prevention of thrombosis was evaluated. METHODS: Totally, 80 vessels including 40 arteries and 40 veins in right and left ears of 20 adult rabbits were enrolled. Seven days after injection of ethanol to rabbit ear vessel, vessel diameter and thrombosis rate post-iced saline challenge were documented and compared to normal saline injection in contralateral ear as a control group. RESULTS: Vessel diameter in both arteries and veins in ethanol group was significantly larger than normal saline control group, and patency rates due to preventive effect of ethanol were also significantly higher in the ethanol group after iced saline challenge. CONCLUSION: Pretreatment with ethanol can enlarge vessel diameter and play a preventive role on thrombosis after iced saline challenge.

Towards green drugs against cestodes: Effectiveness of Pelargonium roseum and Ferula gummosa essential oils and their main component on Echinococcus granulosus protoscoleces.

Cystic echinococcosis is of great public health importance. Surgery is the efficient treatment for this infection. To minimize the risk of cyst intraoperative leakage, using scolicidals is crucial. To date, any efficacious scolicidal without side effect has not been introduced. Since essential oils of Pelargonium roseum and Ferula gummosa have shown several bioactivities, we evaluated their potential against protoscoleces of E. granulosus using albendazole as positive control. Furthermore, chemical composition of both essential oils was analyzed by gas chromatography-mass spectrometry (GC-MS) analyses, and their main constituents were also evaluated for scolicidal activity. Different concentrations of essential oils and their two main constituents were tested for scolicidal activity. Mortality rate was measured by eosin staining. Results of GC-MS revealed citronellol and ß-pinene as the main constituents of P. roseum and F. gummosa essential oils, respectively. After 60 min of exposure to 50 µg/mL of P. roseum and F. gummosa, mean mortality rate of protoscoleces was 100%. However, ß-pinene and citronellol at the same time point with only 10 µg/mL concentrations resulted in approximately higher than 80% mortality. Essential oils of P. roseum and F. gummosa showed significant toxic effect on E. granulosus with 50% lethal concentration (LC50) values of 8.52 and 17.18 µg/mL, respectively. Based on the LC50 values, ß-pinene (2.20 µg/mL) was the most potent scolicidal agent in the present study. The overall toxicity of ß-pinene and citronellol was significantly higher than the whole essential oils of F. gummosa and P. roseum. Based on these results, ß-pinene and citronellol can be considered as candidate ingredients for the development of green scolicidals.

Precision assessment of some supervised and unsupervised algorithms for genotype discrimination in the genus Pisum using SSR molecular data.

For the first time, prediction accuracies of some supervised and unsupervised algorithms were evaluated in an SSR-based DNA fingerprinting study of a pea collection containing 20 cultivars and 57 wild samples. In general, according to the 10 attribute weighting models, the SSR alleles of PEAPHTAP-2 and PSBLOX13.2-1 were the two most important attributes to generate discrimination among eight different species and subspecies of genus Pisum. In addition, K-Medoids unsupervised clustering run on Chi squared dataset exhibited the best prediction accuracy (83.12%), while the lowest accuracy (25.97%) gained as K-Means model ran on FCdb database. Irrespective of some fluctuations, the overall accuracies of tree induction models were significantly high for many algorithms, and the attributes PSBLOX13.2-3 and PEAPHTAP could successfully detach Pisum fulvum accessions and cultivars from the others when two selected decision trees were taken into account. Meanwhile, the other used supervised algorithms exhibited overall reliable accuracies, even though in some rare cases, they gave us low amounts of accuracies. Our results, altogether, demonstrate promising applications of both supervised and unsupervised algorithms to provide suitable data mining tools regarding accurate fingerprinting of different species and subspecies of genus Pisum, as a fundamental priority task in breeding programs of the crop.

Gene identification programs in bread wheat: a comparison study.

Seven ab initio web-based gene prediction programs (i.e., AUGUSTUS, BGF, Fgenesh, Fgenesh+, GeneID, Genemark.hmm, and HMMgene) were assessed to compare their prediction accuracy using protein-coding sequences of bread wheat. At both nucleotide and exon levels, Fgenesh+ was deduced as the superior program and BGF followed by Fgenesh were resided in the next positions, respectively. Conversely, at gene level, Fgenesh with the value of predicting more than 75% of all the genes precisely, concluded as the best ones. It was also found out that programs such as Fgenesh+, BGF, and Fgenesh, because of harboring the highest percentage of correct predictive exons appear to be much more applicable in achieving more trustworthy results, while using both GeneID and HMMgene the percentage of false negatives would be expected to enhance. Regarding initial exon, overall, the frequency of accurate recognition of 3' boundary was significantly higher than that of 5' and the reverse was true if terminal exon is taken into account. Lastly, HMMgene and Genemark.hmm, overall, presented independent tendency against GC content, while the others appear to be slightly more sensitive if GC-poor sequences are employed. Our results, overall, exhibited that to make adequate opportunity in acquiring remarkable results, gene finders still need additional improvements.

Assessment of performance ability of three diagnostic methods for detection of Potato Leafroll virus (PLRV) using different visualizing systems.

To diminish the time required for some diagnostic assays including reverse transcription PCR (RT-PCR), reverse transcription loop-mediated isothermal amplification (RT-LAMP; due to mainly RNA extraction step) and also DAS-ELISA into a minimum level, an innovative immunocapture RT-LAMP (IC-RT-LAMP) and immunocapture reverse transcription (IC/RT-PCR) protocol on the basis of Potato Leafroll virus (PLRV) genome were used and optimized. In this regard, all six IC-RT-LAMP primers (i.e. F3, B3, FIP, BIP, LF and LB) together with IC/RT-PCR primers were designed on the basis of the highly conserved sequence (ORF3) of coat protein gene (GenBank accession number: U73777) of PLRV genome. Even though DAS-ELISA, IC/RT-PCR and IC-RT-LAMP assays could successfully detect positive infected plant samples, considering the time, safety, sensitivity, cost and simplicity, the last one was overall superior. Meanwhile, among five different visual dyes to accurately detect IC-RT-LAMP products, both hydroxynaphthol blue and GeneFinder™ could produce long stable colour change and brightness in a close tube-based approach to prevent cross-contamination risk, concluded eventually as the best ones. Altogether, as IC-RT-LAMP is sensitive, cost-effective, fairly user friendly and also can generate more accurate results than previous diagnostic procedures, we accordingly propose this colorimetric assay as a highly reliable alternative viral recognition system regarding PLRV recognition and probably other viral-based diseases.

Effect of thermal noise on noncontact rack and pinion device.

We study a nanoscale system composed of one corrugated plate (rack) and one corrugated cylinder (pinion) coupled via the lateral Casimir force. We assume that the rack moves uniformly. The axle of the pinion experiences frictional torque and random torque due to a surrounding fluid. We show that even in the presence of thermal noise, the device can work against external loads: The pinion rotates with a nonzero average velocity. The device operation becomes less influenced by the noise as the gap between rack and pinion decreases.

Noncontact rack-pinion-rack device as a differential vibration sensor.

We study a nanoscale system composed of one corrugated cylinder (pinion) placed between two corrugated plates (racks). The pinion and racks have no mechanical contact, but are coupled via the lateral Casimir force-one of the most spectacular consequences of quantum fluctuations of the electromagnetic field. The noncontact design of the device could help with the noteworthy wear problem in nanoscale mechanical systems. We consider the case where both racks undergo harmonic lateral motion. We assume that the amplitude, frequency, and phase of one of the racks are known. We show that probing the pinion motion, one can determine the vibration characteristics of the other rack.

Dynamics of noncontact rack-and-pinion device: Periodic back-and-forth motion of the rack.

We study a nanoscale system composed of one corrugated cylinder (pinion) and one corrugated plate (rack). The pinion and rack have no mechanical contact, but are coupled via the lateral Casimir force. We consider the case where the rack position versus time is a periodic triangular signal. We find that the device can rectify the periodic but nonsinusoidal motion of the rack. Using the typical values of parameters, we find that the pinion rotates with an average angular velocity Ω=1∼100 Hz . Experimental observation of the pinion rotation will show that the quantum vacuum can intermesh the noncontact parts of nanomachines.