ABSTRACT
The COVID-19 pandemic has uncovered the high genetic variability of the SARS-CoV-2 virus and its ability to evade the immune responses that were induced by earlier viral variants. Only a few monoclonal antibodies that have been reported to date are capable of neutralizing a broad spectrum of SARS-CoV-2 variants. Here, we report the isolation of a new broadly neutralizing human monoclonal antibody, iC1. The antibody was identified through sorting the SARS-CoV-1 RBD-stained individual B cells that were isolated from the blood of a vaccinated donor following a breakthrough infection. In vitro, iC1 potently neutralizes pseudoviruses expressing a wide range of SARS-CoV-2 Spike variants, including those of the XBB sublineage. In an hACE2-transgenic mouse model, iC1 provided effective protection against the Wuhan strain of the virus as well as the BA.5 and XBB.1.5 variants. Therefore, iC1 can be considered as a potential component of the broadly neutralizing antibody cocktails resisting the SARS-CoV-2 mutation escape.
Subject(s)
Angiotensin-Converting Enzyme 2 , Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Mice, Transgenic , SARS-CoV-2 , Animals , SARS-CoV-2/immunology , Humans , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Angiotensin-Converting Enzyme 2/immunology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Mice , Antibodies, Viral/immunology , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Pandemics/prevention & control , Betacoronavirus/immunology , Betacoronavirus/genetics , Broadly Neutralizing Antibodies/immunology , Disease Models, Animal , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Pneumonia, Viral/prevention & control , Coronavirus Infections/immunology , Coronavirus Infections/virology , Coronavirus Infections/prevention & controlABSTRACT
New nitrosonium manganese(II) nitrate, (NO)Mn6(NO3)13, has been synthesized and structurally characterized. In the temperature range of 45-298 K, the crystal is hexagonal (centrosymmetric sp. gr. P63/m). Mn2+ ions are assembled into tubes along axis c with both NO3- filling and coating. The nitrosonium cation is located in the framework cavity and is disordered by a 3-fold axis. At the temperature TS1 = 190 K, a structural phase transition related to the libration of the intertube NO3 group and a small variation of Mn polyhedron is observed. Moreover, the anomalies in physical properties of (NO)Mn6(NO3)13 allow suggesting that ordering of NO+ units occurs at low temperatures. The antiferromagnetic ordering in this compound is preceded by the formation of a short-range correlation regime at about 25 K and takes place in two steps at TN1 = 12.0 K and TN2 = 8.4 K.
ABSTRACT
The emergence of SARS-CoV-2 mutant variants has posed a significant challenge to both the prevention and treatment of COVID-19 with anti-coronaviral neutralizing antibodies. The latest viral variants demonstrate pronounced resistance to the vast majority of human monoclonal antibodies raised against the ancestral Wuhan variant. Less is known about the susceptibility of the evolved virus to camelid nanobodies developed at the start of the pandemic. In this study, we compared nanobody repertoires raised in the same llama after immunization with Wuhan's RBD variant and after subsequent serial immunization with a variety of RBD variants, including that of SARS-CoV-1. We show that initial immunization induced highly potent nanobodies, which efficiently protected Syrian hamsters from infection with the ancestral Wuhan virus. These nanobodies, however, mostly lacked the activity against SARS-CoV-2 omicron-pseudotyped viruses. In contrast, serial immunization with different RBD variants resulted in the generation of nanobodies demonstrating a higher degree of somatic mutagenesis and a broad range of neutralization. Four nanobodies recognizing distinct epitopes were shown to potently neutralize a spectrum of omicron variants, including those of the XBB sublineage. Our data show that nanobodies broadly neutralizing SARS-CoV-2 variants may be readily induced by a serial variant RBD immunization.
ABSTRACT
SARS-CoV-2 has a relatively high mutation rate, with the frequent emergence of new variants of concern (VOCs). Each subsequent variant is more difficult to neutralize by the sera of vaccinated individuals and convalescents. Some decrease in neutralizing activity against new SARS-CoV-2 variants has also been observed in patients vaccinated with Gam-COVID-Vac. In the present study, we analyzed the interplay between the history of a patient's repeated exposure to SARS-CoV-2 antigens and the breadth of neutralization activity. Our study includes four cohorts of patients: Gam-COVID-Vac booster vaccinated individuals (revaccinated, RV), twice-infected unvaccinated individuals (reinfected, RI), breakthrough infected (BI), and vaccinated convalescents (VC). We assessed S-protein-specific antibody levels and the ability of sera to neutralize lentiviral particles pseudotyped with Spike protein from the original Wuhan variant, as well as the Omicron variants BA.1 and BA.4/5. Individuals with hybrid immunity (BI and VC cohorts) exhibited significantly higher levels of virus-binding IgG and enhanced breadth of virus-neutralizing activity compared to individuals from either the revaccination or reinfection (RV and RI) cohorts. These findings suggest that a combination of infection and vaccination, regardless of the sequence, results in significantly higher levels of S-protein-specific IgG antibodies and the enhanced neutralization of SARS-CoV-2 variants, thereby underscoring the importance of hybrid immunity in the context of emerging viral variants.
ABSTRACT
Development of a fast and accurate pesticide analysis system is a challenging task, as a large amount of commonly used pesticide has negative effects on humans' health. Detection of pesticide residues is crucial for food safety management and environmental protection. Aptamersâshort single-stranded oligonucleotides (RNA or DNA) selected by aptamer selection method SELEXâcan selectively bind to their target pesticide molecules with high affinity. Thus, in the present study, we developed an electrochemical biosensor based on aptamers to detect the commonly used pesticide, glyphosate. Carbon fibers were used as the platform to assemble polyelectrolyte layers with the incorporated aptamers selectively binding with glyphosate molecules for electrochemical detection. The best limit of detection of 0.3 µM was achieved at open-circuit potential measurements, which is comparable to the current need in detection of glyphosate. The developed method can be implemented into existing systems for the determination of pesticides on farms to control residual concentrations of glyphosate in soil and water.
Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Pesticides , Humans , Aptamers, Nucleotide/chemistry , Layer-by-Layer Nanoparticles , DNA , Biosensing Techniques/methodsABSTRACT
Anhydrous copper tellurite sulfate, Cu3TeO3(SO4)2, has been synthesized via vapor transport reactions in sealed silica glass ampoules. In measurements of magnetization M, magnetic susceptibility χ, specific heat Cp and X-band electron spin resonance, a long-range antiferromagnetic order at TN = 13 K and an H-T magnetic phase diagram have been established. One-third of Cu2+ ions were found to form magnetically silent dimers. A peak in dielectric permittivity ε, which accompanies the Néel order, allows considering Cu3TeO3(SO4)2 as a magnetoelectric multiferroic material of the second type. Density functional theory calculations provided estimations of leading exchange interaction parameters.
ABSTRACT
The emerging novel class of two-dimensional materials - MÐ¥enes - have attracted significant research attention. However, there are only few reports on using the most prominent member of the MXene family, Ti3 C2 Tx , as an active material for memristive devices within a polyelectrolyte matrix and its deposition on inert electrodes like ITO and Pt. In this study, we systematically investigate Ti3 C2 Tx MXenes synthesized with two classical delamination agents, such as lithium chloride and tetramethylammonium hydroxide, to identify the most suitable candidate for memristive device applications. The characteristics of memristors based on the hybrid structures consisting of MXene-polyelectrolyte multilayers, specifically polyethyleneimine (PEI) and poly(sodium 4-styrenesulfonate) (PSS) are explored. The PEI(MXene)/PSS memristor exhibits a voltage threshold (VSET/RESET ) range of 1.5-2.0â V, enabling the transition from a high-resistive state (HRS) to a low-resistive state (LRS), along with a significant current switching ratio of approximately two orders of magnitude. The observed VSET/RESET difference of approximately 4â V is further supported by density functional theory (DFT) calculated redox potential. These findings underscore the potential of polyelectrolyte-based memristors, such as the in PEI-Ti3 C2 Tx -PSS system, in facilitating the development of highly functional, self-assembled memristive devices with diverse applications.
ABSTRACT
Over the past decade, CAR T cell therapy for patients with B cell malignancies has evolved from an experimental technique to a clinically feasible option. To date, four CAR T cell products specific for a B cell surface marker, CD19, have been approved by the FDA. Despite the spectacular rates of complete remission in r/r ALL and NHL patients, a significant proportion of patients still relapse, frequently with the CD19 low/negative tumor phenotype. To address this issue, additional B cell surface molecules such as CD20 were proposed as targets for CAR T cells. Here, we performed a side-by-side comparison of the activity of CD20-specific CAR T cells based on the antigen-recognition modules derived from the murine antibodies, 1F5 and Leu16, and from the human antibody, 2F2. Whereas CD20-specific CAR T cells differed from CD19-specific CAR T cells in terms of subpopulation composition and cytokine secretion, they displayed similar in vitro and in vivo potency.
Subject(s)
Antigens, CD20 , Immunotherapy, Adoptive , Animals , Humans , Mice , Cytotoxicity, Immunologic , Immunotherapy, Adoptive/methods , T-Lymphocytes/immunologyABSTRACT
Terbium tritelluride, TbTe3, orders antiferromagnetically in three steps at TN1 = 6.7 K, TN2 = 5.7 K, and TN3 = 5.4 K, preceded by a correlation hump in magnetic susceptibility at T* ~8 K. Combining thermodynamic, i.e., specific heat Cp and magnetization M, and transport, i.e., resistance R, measurements we established the boundaries of two commensurate and one charge density wave modulated phases in a magnetic field oriented along principal crystallographic axes. Based on these measurements, the magnetic phase diagrams of TbTe3 at Hâa, Hâb and Hâc were constructed.
ABSTRACT
The appearance of electrically neutral water molecules in the structure of cobalt dinitrate dihydrate, Co(NO3)2â 2H2O, drastically changes its magnetic properties as compared to its waterless counterpart, Co(NO3)2. The title compound shows Ising-like behavior reflected in its thermodynamic properties. It experiences long-range antiferromagnetic order at TN = 20.5 K and metamagnetic transition at µ0HC = 0.76 T. First-principles calculations produce the values of leading exchange interactions J1 ~ 10 K and J2 ~ 0.5 K and single-ion anisotropy D ~ 1 K which allows us to consider Co(NO3)2â 2H2O as a quasi-two-dimensional magnetic system.
ABSTRACT
Immune evasion of SARS-CoV-2 undermines current strategies tocounteract the pandemic, with the efficacy of therapeutic virus-neutralizing monoclonal antibodies (nAbs) being affected the most. In this work, we asked whether two previously identified human cross-neutralizing nAbs, iB14 (class VH1-58) and iB20 (class VH3-53/66), are capable of neutralizing the recently emerged Omicron (BA.1) variant. Both nAbs were found to bind the Omicron RBD with a nanomolar affinity, yet they displayed contrasting functional features. When tested against Omicron, the neutralizing activity of iB14 was reduced 50-fold, whereas iB20 displayed a surprising increase in activity. Thus, iB20 is a unique representative of the VH3-53/66-class of nAbs in terms of breadth of neutralization, which establishes it as a candidate for COVID-19 therapy and prophylactics.
ABSTRACT
Sufficient boron-10 isotope (10B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered 10B-containing borophenylalanine (BPA) to maintain a high boron tumor concentration during neutron irradiation after a single injection has been partially solved by its continuous infusion; however, its lack of persistence has driven the development of new compounds that overcome the imperfections of BPA. We propose using elemental boron nanoparticles (eBNPs) synthesized by cascade ultrasonic dispersion and destruction of elemental boron microparticles and stabilized with hydroxyethylcellulose (HEC) as a core component of a novel boron drug for BNCT. These HEC particles are stable in aqueous media and show no apparent influence on U251, U87, and T98G human glioma cell proliferation without neutron beam irradiation. In BNCT experiments, cells incubated with eBNPs or BPA at an equivalent concentration of 40 µg 10B/mL for 24 h or control cells without boron were irradiated at an accelerator-based neutron source with a total fluence of thermal and epithermal neutrons of 2.685, 5.370, or 8.055 × 1012/cm2. The eBNPs significantly reduced colony-forming capacity in all studied cells during BNCT compared to BPA, verified by cell-survival curves fit to the linear-quadratic model and calculated radiobiological parameters, though the effect of both compounds differed depending on the cell line. The results of our study warrant further tumor targeting-oriented modifications of synthesized nanoparticles and subsequent in vivo BNCT experiments.
ABSTRACT
We synthesized single crystals of Na0.55Ni6(OH)3(H0.61PO4)4 (I) and polycrystals of (Na, Ni)0.64Ni5.68(OH)3(H0.67PO4)4 (II) with ellenbergerite-like structures using the hydrothermal method. The phases crystallize in the hexagonal space group P63mc with the following unit cell parameters: a = 12.5342(1) Å, c = 4.9470(1) Å, and V = 673.08(2) Å3 for I; a = 12.4708(2) Å, c = 4.9435(2) Å, and V = 665.82(2) Å3 for II; and Z = 2. Their crystal structures are based on a 3D framework built from NiO6 octahedra and PO4 tetrahedra. The difference between I and II lies in the way the structural channels are filled along the [001] direction. These channels accommodate segments of Na- and (Na, Ni)-centered chains of face-sharing octahedra in the structures I and II, respectively. The magnetic susceptibility χ and the specific heat Cp evidence pronounced low-dimensional magnetic behavior at elevated temperatures and the formation of the weakly ferromagnetic long-range order at TNI = 61 K and TNII = 63 K. Analysis of the χ(T) data within both chain and dimer spin models allows the estimation of the leading exchange interaction parameters in the compounds under study.
ABSTRACT
Novel copper phosphate chloride has been obtained under middle-temperature hydrothermal conditions. Its crystal structure was established based on the low-temperature X-ray diffraction data: Na2Li0.75(Cs,K)0.5[Cu5(PO4)4Cl]·3.5(H2O,OH), sp. gr. C2/m, a = 19.3951(8) Å, b = 9.7627(3) Å, c = 9.7383(4) Å, ß = 99.329(4)°, T = 150 K, MoKα (λ = 0.71073 Å), R = 0.049. The crystal structure includes tetrameric copper clusters as the main building blocks, which are built of four CuO4Cl pyramids sharing apical Cl vertices. The clusters are combined through phosphate groups and additional copper-centered polyhedra to form two mostly ordered periodic layers. Between the layers and inside the framework channels, alkali ions, H2O molecules, or OH groups are statistically distributed. Na2Li0.75(Cs,K)0.5[Cu5(PO4)4Cl]·3.5(H2O,OH) is a synthetic modification of a sampleite-polymorph of the lavendulan mineral group and represents a new member in a mero-plesiotype series of copper phosphates and arsenates, for which the crystal structures contain two-periodic [Cu4X(TO4)4]∞ modules (T = As, P; X = Cl, O). Magnetically, this phase exhibits the phase transition at TC = 6.5 K, below which it possesses a weak ferromagnetic moment.
ABSTRACT
Biopolymers and their derivatives are materials with increasing interest for industry and especially for sustainable engineering development. Among such kind of materials, carbohydrate polymer like highly deacetylated chitin (chitosan) is widely used for a wide range of applications, including material and biomedical developments. The majority of industrially produced chitosan is based on chitin extracted from crustacean exoskeleton. However, with increase of interest on this material, chitosan's production will rapidly become insufficient and other species should be investigated as new sources of chitosan. In the present work, we focus on the preparation of chitosan from giant dung beetles (Genus Heliocopris, Hope, 1838). This genus was chosen to show the possibility to take animals that develop and leave near dejection and valuate them for material applications. This work includes all the chitosan extraction procedures, chitosan characterisation IR, SEM, NMR, ash content, and deacetylation degree. Finally, the prepared carbohydrate polymer is used to form hydrogel. The prepared gel has been characterised and used for 3D printing, to show the compatibility of extracted chitosan with biomaterial application.
Subject(s)
Chitosan , Coleoptera , Animals , Chitin/chemistry , Chitosan/chemistry , Hydrogels , Printing, Three-DimensionalABSTRACT
The polyepitope strategy is promising approach for successfully creating a broadly protective flu vaccine, which targets T-lymphocytes (both CD4+ and CD8+) to recognise the most conserved epitopes of viral proteins. In this study, we employed a computer-aided approach to develop several artificial antigens potentially capable of evoking immune responses to different virus subtypes. These antigens included conservative T-cell epitopes of different influenza A virus proteins. To design epitope-based antigens we used experimentally verified information regarding influenza virus T-cell epitopes from the Immune Epitope Database (IEDB) (http://www.iedb.org). We constructed two "human" and two "murine" variants of polyepitope antigens. Amino acid sequences of target polyepitope antigens were designed using our original TEpredict/PolyCTLDesigner software. Immunogenic and protective features of DNA constructs encoding "murine" target T-cell immunogens were studied in BALB/c mice. We showed that mice groups immunised with a combination of computer-generated "murine" DNA immunogens had a 37.5% survival rate after receiving a lethal dose of either A/California/4/2009 (H1N1) virus or A/Aichi/2/68 (H3N2) virus, while immunisation with live flu H1N1 and H3N2 vaccine strains provided protection against homologous viruses and failed to protect against heterologous viruses. These results demonstrate that mechanisms of cross-protective immunity may be associated with the stimulation of specific T-cell responses. This study demonstrates that our computer-aided approach may be successfully used for rational designing artificial polyepitope antigens capable of inducing virus-specific T-lymphocyte responses and providing partial protection against two different influenza virus subtypes.Communicated by Ramaswamy H. Sarma.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza, Human , Animals , Antigens, Viral/genetics , Epitopes, T-Lymphocyte , Humans , Influenza A Virus, H3N2 Subtype , Mice , Mice, Inbred BALB C , T-LymphocytesABSTRACT
In the absence of virus-targeting small-molecule drugs approved for the treatment and prevention of COVID-19, broadening the repertoire of potent SARS-CoV-2-neutralizing antibodies represents an important area of research in response to the ongoing pandemic. Systematic analysis of such antibodies and their combinations can be particularly instrumental for identification of candidates that may prove resistant to the emerging viral escape variants. Here, we isolated a panel of 23 RBD-specific human monoclonal antibodies from the B cells of convalescent patients. A surprisingly large proportion of such antibodies displayed potent virus-neutralizing activity both in vitro and in vivo. Four of the isolated nAbs can be categorized as ultrapotent with an apparent IC100 below 16 ng/mL. We show that individual nAbs as well as dual combinations thereof retain activity against currently circulating SARS-CoV-2 variants of concern (such as B.1.1.7, B.1.351, B.1.617, and C.37), as well as against other viral variants. When used as a prophylactics or therapeutics, these nAbs could potently suppress viral replication and prevent lung pathology in SARS-CoV-2-infected hamsters. Our data contribute to the rational development of oligoclonal therapeutic nAb cocktails mitigating the risk of SARS-CoV-2 escape.
ABSTRACT
Boron neutron capture therapy (BNCT) is an anticancer modality realized through 10B accumulation in tumor cells, neutron irradiation of the tumor, and decay of boron atoms with the release of alpha-particles and lithium nuclei that damage tumor cell DNA. As high-LET particle release takes place inside tumor cells absorbed dose calculations are difficult, since no essential extracellular energy is emitted. We placed gold nanoparticles inside tumor cells saturated with boron to more accurately measure the absorbed dose. T98G cells accumulated ~50 nm gold nanoparticles (AuNPs, 50 µg gold/mL) and boron-phenylalanine (BPA, 10, 20, 40 µg boron-10/mL), and were irradiated with a neutron flux of 3 × 108 cm-2s-1. Gamma-rays (411 keV) emitted by AuNPs in the cells were measured by a spectrometer and the absorbed dose was calculated using the formula D = (k × N × n)/m, where D was the absorbed dose (GyE), k-depth-related irradiation coefficient, N-number of activated gold atoms, n-boron concentration (ppm), and m-the mass of gold (g). Cell survival curves were fit to the linear-quadratic (LQ) model. We found no influence from the presence of the AuNPs on BNCT efficiency. Our approach will lead to further development of combined boron and high-Z element-containing compounds, and to further adaptation of isotope scanning for BNCT dosimetry.
ABSTRACT
We used nanoparticles which possess simultaneously active (antimicrobial, UV-protective and antioxidant) and smart (temperature sensing) properties. The nanoparticles (2Rh = 450 nm, PDI = 0.118 ± 0.014, ζ-potential = 21 mV and Tg = 8 ± 1 °C) are based on polyethylene glycol (PEG)/methyl cellulose (MC) core with anthocyanidin and sodium acetate, and chitosan/gallotannin-based shell. The core of nanoparticles acts as a temperature indicator, changing its color from colorless into deep purple at 8 °C, while the shell provides antimicrobial (due to chitosan), UV-protective and antioxidant (due to gallotannin) effects. We incorporated these nanoparticles into the chitosan matrix. The coatings demonstrated improved mechanical and barrier properties compared with the pure chitosan coating. The elaborated coatings pronouncedly improve the shelf-life of Ricotta cheese. Moreover, they serve as thermo indicators, which warn about cheese storage at an unacceptable temperature. Thus, we developed new coatings in which all properties are enabled by a single type of nanoparticles.
Subject(s)
Anti-Infective Agents/chemistry , Chitosan/chemistry , Food Packaging/methods , Nanoparticles/chemistry , Anti-Infective Agents/pharmacology , Antioxidants/chemistry , Cheese/analysis , Escherichia coli/drug effects , Fungi/drug effects , Hydrolyzable Tannins/chemistry , Methylcellulose/chemistry , Nanoparticles/toxicity , Polyethylene Glycols/chemistry , Staphylococcus aureus/drug effects , Temperature , Tensile StrengthABSTRACT
In the present work, we demonstrate that alkylation of chitosan by alkyl halides, aza-Michael reaction with chitosan, and AdN-E reaction of chitosan with aldehydes can be efficiently mediated by ultrasound. An optimization of ultrasonic irradiation parameters allowed us to (i) accelerate the rate of the reactions dramatically, (ii) achieve high selectivity, and (iii) preserve integrity of the polysaccharide backbone avoiding its depolymerization. We evaluated antibacterial/antifungal and transfection activity of 8 different derivatives of chitosan and their based nanoparticles in vitro. Moreover, we studied antibacterial activity of the most efficient polymer and their based nanoparticles in vivo. The tested polymer proved to be superior to reference commercial antibiotics ampicillin and gentamicin.