Current State of the Development of Next-Generation Vaccines against Ebola Virus Disease

Representative of Ebolavirus gender, Filoviridae family, Ebola virus is an etiological agent of particularly dangerous viral fever, the lethality of which comes up to 88 %. According to the leading specialists and experts in the sphere, vaccination is the most effective and cost-efficient method for the protection from epidemic spread. Objective of the review is to analyze current state of the development of next generation vaccines against Ebola fever. It is established that focus areas of the activities are the construction of vaccines on the basis of alpha-virus replicons, virus-like particles, and the development of DNA-vaccines and vector recombinant vaccines. The paper discusses the most significant achievements in the sphere of obtainment of potent therapies for prophylaxis as regards Ebola fever. To date manufactured, using various approaches, have been the next-generation vaccine preparations, for a number of which high protective capacity is demonstrated in the course of experiments on the nonhuman primates. The most advanced and prospective prototype is the vector recombinant vesicular stomatitis virus-based vaccine

Finite size and intrinsic field effect on the polar-active properties of the ferroelectric-semiconductor heterostructures

Using Landau-Ginzburg-Devonshire approach we calculated the equilibrium distributions of electric field, polarization and space charge in the ferroelectric-semiconductor heterostructures containing proper or incipient ferroelectric thin films. The role of the polarization gradient and intrinsic surface energy, interface dipoles and free charges on polarization dynamics are specifically explored. The intrinsic field effects, which originated at the ferroelectric-semiconductor interface, lead to the surface band bending and result into the formation of depletion space-charge layer near the semiconductor surface. During the local polarization reversal (caused by the inhomogeneous electric field induced by the nanosized tip of the Scanning Probe Microscope (SPM) probe) the thickness and charge of the interface layer drastically changes, it particular the sign of the screening carriers is determined by the polarization direction. Obtained analytical solutions could be extended to analyze polarization-mediated electronic transport.Comment: 35 pages, 12 figures, 1 table, 2 appendices, to be submitted to Phys. Rev.

Suppression of Octahedral Tilts and Associated Changes of Electronic Properties at Epitaxial Oxide Heterostructure Interfaces

Epitaxial oxide interfaces with broken translational symmetry have emerged as a central paradigm behind the novel behaviors of oxide superlattices. Here, we use scanning transmission electron microscopy to demonstrate a direct, quantitative unit-cell-by-unit-cell mapping of lattice parameters and oxygen octahedral rotations across the BiFeO3-La0.7Sr0.3MnO3 interface to elucidate how the change of crystal symmetry is accommodated. Combined with low-loss electron energy loss spectroscopy imaging, we demonstrate a mesoscopic antiferrodistortive phase transition and elucidate associated changes in electronic properties in a thin layer directly adjacent to the interface

Conductivity of twin walls - surface junctions in ferroelastics: interplay of deformation potential, octahedral rotations, improper ferroelectricity and flexoelectric coupling

Electronic and structural phenomena at the twin domain wall-surface junctions in the ferroelastic materials are analyzed. Carriers accumulation caused by the strain-induced band structure changes originated via the deformation potential mechanism, structural order parameter gradient, rotostriction and flexoelectric coupling is explored. Approximate analytical results show that inhomogeneous elastic strains, which exist in the vicinity of the twin walls - surface junctions due to the rotostriction coupling, decrease the local band gap via the deformation potential and flexoelectric coupling mechanisms. This is the direct mechanism of the twin walls static conductivity in ferroelastics and, by extension, in multiferroics and ferroelectrics. On the other hand, flexoelectric and rotostriction coupling leads to the appearance of the improper polarization and electric fields proportional to the structural order parameter gradient in the vicinity of the twin walls - surface junctions. The "flexo-roto" fields leading to the carrier accumulation are considered as indirect mechanism of the twin walls conductivity. Comparison of the direct and indirect mechanisms illustrates complex range of phenomena directly responsible for domain walls static conductivity in materials with multiple order parameters.Comment: 35 pages, 11 figures, 3 table, 3 appendices Improved set of rotostriction coefficients are used in calculation

A novel factor I activity in Nipah virus inhibits human complement pathways through cleavage of C3b

Complement is an innate immune system that most animal viruses must face during natural infections. Given that replication and dissemination of the highly pathogenic Nipah virus (NiV) include exposure to environments rich in complement factors, we tested the in vitro sensitivity of NiV to complement-mediated neutralization. Here we show that NiV was completely resistant to in vitro neutralization by normal human serum (NHS). Treatment of purified NiV with NHS activated complement pathways, but there was very little C3 deposition on virus particles. In in vitro reconstitution experiments, NiV particles provided timeand dose-dependent factor I-like protease activity capable of cleaving C3b into inactive C3b (iC3b). NiV-dependent inactivation of C3b only occurred with the cofactors factor H and soluble CR1 but not with CD46. Purified NiV particles did not support C4b cleavage. Electron microscopy of purified NiV particles showed immunogold labeling with anti-factor I antibodies. Our results suggest a novel mechanism by which NiV evades the human complement system through a unique factor I-like activity

Roto-flexoelectric coupling impact on the phase diagrams and pyroelectricity of thin SrTiO3 films

The influence of the flexoelectric and rotostriction coupling on the phase diagrams of ferroelastic-quantum paraelectric SrTiO3 films was studied using Landau-Ginzburg-Devonshire (LGD) theory. The phase diagrams in coordinates temperature - film thickness were calculated for different epitaxial misfit strains. Tensile misfit strains stimulate appearance of the spontaneous out-of-plane structural order parameter (displacement vector of an appropriate oxygen atom from its cubic position) in the structural phase. Compressive misfit strains stimulate appearance of the spontaneous in-plane structural order parameter. Gradients of the structural order parameter components, which inevitably exist in the vicinity of film surfaces due to the termination and symmetry breaking, induce improper polarization and pyroelectric response via the flexoelectric and rotostriction coupling mechanism. Flexoelectric and rotostriction coupling results in the roto-flexoelectric field that is antisymmetric inside the film, small in the central part of the film, where the gradients of the structural parameter are small, and maximal near the surfaces, where the gradients of the structural parameter are highest. The field induces improper polarization and pyroelectric response. Penetration depths of the improper phases (both polar and structural) can reach several nm from the film surfaces. An improper pyroelectric response of thin films is high enough to be registered with planar-type electrode configurations by conventional pyroelectric methods.Comment: 35 pages, 9 figures, 1 appendix, 1 tabl

In situ observation of oxygen vacancy dynamics and ordering in the epitaxial LaCoO3 system

Vacancy dynamics and ordering underpin the electrochemical functionality of complex oxides and strongly couple to their physical properties. In the field of the epitaxial thin films, where connection between chemistry and film properties can be most clearly revealed, the effects related to oxygen vacancies are attracting increasing attention. In this article, we report a direct, real-time, atomic level observation of the formation of oxygen vacancies in the epitaxial LaCoO3 thin films and heterostructures under the influence of the electron beam utilizing scanning transmission electron microscopy (STEM). In the case of LaCoO3/SrTiO3 superlattice, the formation of the oxygen vacancies is shown to produce quantifiable changes in the interatomic distances, as well as qualitative changes in the symmetry of the Co sites manifested as off-center displacements. The onset of these changes was observed in both the [100]pc and [110]pc orientations in real time. Additionally, annular bright field images directly show the formation of oxygen vacancy channels along [110]pc direction. In the case of 15 u.c. LaCoO3 thin film, we observe the sequence of events during beam-induced formation of oxygen vacancy ordered phases and find them consistent with similar processes in the bulk. Moreover, we record the dynamics of the nucleation, growth, and defect interaction at the atomic scale as these transformations happen. These results demonstrate that we can track dynamic oxygen vacancy behavior with STEM, generating atomic-level quantitative information on phase transformation and oxygen diffusion

The Flow Cytometry Study of Cellular Immunity in Rhesus Monkeys after Experimental Infection with SARS CoV 2 Virus

Cellular immunity plays an important role in the pathogenesis and formation of protective immune defense against the SARS‑CoV‑2 virus.The aim of the work was to study the cellular immunity of rhesus monkeys applying flow cytometry after experimental infection with the SARS‑CoV‑2 virus.Materials and methods. Male rhesus monkeys were intranasally inoculated with the SARS‑CoV‑2 virus, Isolate B strain and hCoV-19/Russia/SP48-1226/2020 strain (abbreviated name U-2), at a dose of 5.0 lg PFU. Using flow cytometry, the levels of 21 populations/subpopulations of mononuclear cells in the peripheral blood of animals were determined before experimental infection with the pathogen and on day 14 after infection. SARS‑CoV‑2 coronavirus RNA was assessed using real-time polymerase chain reaction. Determination of the titer of virus-neutralizing antibodies to the SARS‑CoV‑2 virus in the blood sera of animals was conducted through neutralization test evaluating the ability to suppress negative colonies.Results and discussion. Infection with Isolate B strain culture has led to an increase in the relative content of total T-lymphocytes (p˂0.2), cytotoxic T-lymphocytes (p˂0.1), as well as monocytes expressing the early activation marker CD25 (p˂0.2). The decrease in levels has been observed for total B-lymphocytes (p˂0.2) and T-helper cells (p˂0.1). Infection with the U-2 strain culture revealed an increase in the relative content of monocytes expressing the early activation marker CD25 (p˂0.2). Thus, for the first time in the Russian Federation, flow cytometry was used to study the cellular immunity of rhesus monkeys before and after experimental infection with the SARS‑CoV‑2 virus. The obtained information can be used for studying the pathogenesis of SARS‑CoV‑2 infection, course, and outcome of the disease, and developing strategies for vaccination and treatment