Designing and development of multi-epitope chimeric vaccine against Helicobacter pylori by exploring its entire immunogenic epitopes: an immunoinformatic approach.

BACKGROUND: Helicobacter pylori is a prominent causative agent of gastric ulceration, gastric adenocarcinoma and gastric lymphoma and have been categorised as a group 1 carcinogen by WHO. The treatment of H. pylori with proton pump inhibitors and antibiotics is effective but also leads to increased antibiotic resistance, patient dissatisfaction, and chances of reinfection. Therefore, an effective vaccine remains the most suitable prophylactic option for mass administration against this infection. RESULTS: We modelled a multi-chimera subunit vaccine candidate against H. pylori by screening its secretory/outer membrane proteins. We identified B-cell, MHC-II and IFN-γ-inducing epitopes within these proteins. The population coverage, antigenicity, physiochemical properties and secondary structure were evaluated using different in-silico tools, which showed it can be a good and effective vaccine candidate. The 3-D construct was predicted, refined, validated and docked with TLRs. Finally, we performed the molecular docking/simulation and immune simulation studies to validate the stability of interaction and in-silico cloned the epitope sequences into a pET28b(+) plasmid vector. CONCLUSION: The multiepitope-constructed vaccine contains T- cells, B-cells along with IFN-γ inducing epitopes that have the property to generate good cell-mediated immunity and humoral response. This vaccine can protect most of the world's population. The docking study and immune simulation revealed a good binding with TLRs and cell-mediated and humoral immune responses, respectively. Overall, we attempted to design a multiepitope vaccine and expect this vaccine will show an encouraging result against H. pylori infection in in-vivo use.

Effect of Mn doping on the electronic and optical properties of Dy2Ti2O7: a combined spectroscopic and theoretical study.

Electronic and optical studies on Dy2Ti2-MnxO7(x= 0.00, 0.05, 0.10, 0.15, & 0.20) have been presented through both, theoretical (density functional theory (DFT) calculations) and experimental (ultraviolet-visible absorption and photoluminescence emission spectroscopy) approaches. DFT calculations were employed considering the local density approximation (LDA) and LDA-1/2 for exchange-correlation interactions. Computed crystallographic parameters and energy band-gap using theoretical formulations are in good agreement with experimental results. The band-gap value obtained through the LDA-1/2 approach indicates insulated ground state of Dy2Ti2-xMnxO7(x= 0.00, 0.05, 0.10, 0.15, 0.20) system. Experimentally obtained band gap value reduces from 3.82 eV to 2.45 eV with increase in positive chemical pressure asxincreases from 0 to 0.20. Reduction in band gap value is attributed to the fact that there exists a lack of hybridization between the O-2p orbital and Ti-3d orbital, which is well correlated with the crystallographic data. Jahn-Teller effect is likely to be responsible for the presence of a mixed state of Mn (explained using x-ray photoelectron spectroscopy results), resulting in the intermediate Mn state between the valence band and the conduction band with immediate inclusion of Mn at Ti site in Dy2Ti2-xMnxO7system.

Role of chemical pressure on optical and electronic structure of Ho2Ge x Ti2-x O7.

Chemical pressure plays a crucial role in determining the electronic properties of the quantum materials. Investigation of electronic structure of Ho2Ge x Ti2-x O7 (x = 2, 1.9, 1.75, 1.5 1, 0.5, 0.25, 0.1 and 0) series has been performed. Pyrochlore and Pyrogermanate, Re2B2O7 (Re = Ho3+, B = Ti4+ and Ge4+; rare earth titanates and germanates), substituted with increasing amount of Ge4+ at the Ti4+ site and vice versa develops structural distortions. Distinct shrinkage effect has been established in the Ho2Ti2O7 matrix upon Ge+4 substitutions at B site, resulting in the modification of band gap value. Band gap of 5.24 eV drastically drops to 3.92 eV with immediate Ti4+ substitution in Ho2Ge2O7. Electronic states of Ho3+ (4f forbidden transitions) had also been identified. We observe favored sub level transition (Specific Stark component) corresponding to5F5 to 5I8 electronic transition for Ho3+ at λ exc. = 450 nm. The upper valence band consisted of O 2p state hybridized with Ho 5p and Ti and Ge 4p states and conduction band primarily formed by Ho 5d state hybridized with Ti 3d and Ge 4d states as obtained from density of states (DOS) calculations. Strong hybridization between Ho 5p1/2 and Ti 3p orbital upon Ti4+ inclusion in Ho2Ge2O7 has been observed through both theoretical studies using LDA-1/2 and UV-Vis, photoluminescence, ultraviolet photoelectron spectroscopy (UPS) and x-ray photoelectron spectroscopy. The evolution of total DOS of all studied composition shows that valence band edge is more sensitive than conduction band to composition. These results provide chemical pressure as an excellent tool to tailor the band gap and fine tune the intermediate electronic states in Ho2Ge x Ti2-x O7.

Strategic Development of a Next-Generation Multi-Epitope Vaccine To Prevent Nipah Virus Zoonotic Infection.

Nipah virus (NiV) is an emerging zoonotic pathogen, reported for the recent severe outbreaks of encephalitis and respiratory illness in humans and animals, respectively. Many antiviral drugs have been discovered to inhibit this pathogen, but none of them were that much efficient. To overcome the complications associated with this severe pathogenic virus, we have designed a multi-epitope subunit vaccine using computational immunology strategies. Identification of structural and nonstructural proteins of Nipah virus assisted in the vaccine designing. The selected proteins are known to be involved in the survival of the virus. The antigenic binders (B-cell, HTL, and CTL) from the selected proteins were prognosticated. These antigenic binders will be able to generate the humoral as well as cell-mediated immunity. All the epitopes were united with the help of suitable linkers and with an adjuvant at the N-terminal of the vaccine, for the enhancement of immunogenicity. The physiological characterization, along with antigenicity and allergenicity of the designed vaccine candidates, was estimated. The 3D structure prediction and its validation were performed. The validated vaccine model was then docked and simulated with the TLR-3 receptor to check the stability of the docked complex. This next-generation approach will provide a new vision for the development of a high immunogenic vaccine against the NiV.

Combinatorial screening algorithm to engineer multiepitope subunit vaccine targeting human T-lymphotropic virus-1 infection.

Human T-lymphotropic virus (HTLV), the first human retrovirus has been discovered which is known to cause the age-old assassinating disease HTLV-1 associated myelopathy. Cancer caused by this virus is adult T cell leukemia/lymphoma which targets 10-20 million throughout the world. The effect of this virus extends to the fact that it causes chronic disease to the spinal cord resulting in loss of sensation and further causes blood cancer. So, to overcome the complications, we designed a subunit vaccine by the assimilation of B-cell, cytotoxic T-lymphocyte , and helper T-lymphocyte epitopes. The epitopes were joined together along with adjuvant and linkers and a vaccine was fabricated which was further subjected to 3D modeling. The physiochemical properties, allergenicity, and antigenicity were evaluated. Molecular docking and dynamics were performed with the obtained 3D model against toll like receptor (TLR-3) immune receptor. Lastly, in silico cloning was performed to ensure the expression of the designed vaccine in pET28a(+) expression vector. The future prospects of the study entailed the in vitro and in vivo experimental analysis for evaluating the immune response of the designed vaccine construct.

Circulating MicroRNAs: Potential and Emerging Biomarkers for Diagnosis of Human Infectious Diseases.

MicroRNAs (miRNAs) are evolutionary conserved, small non-coding RNA with size ranging from 19 to 24 nucleotides. They endogenously regulate the gene expression at the post transcriptional level either through translation repression or mRNA degradation. MiRNAs have shown the potential to be used as a biomarker for the diagnosis, prognosis, and therapy of infectious diseases. Many miRNAs have shown significantly altered expression during infection. The altered expression of miRNA level in an infected human can be identified by the use of advanced diagnostic tools. In this review, we have highlighted the use of miRNA as an emerging tool for the identification of the human infectious disease. Till date, several miRNAs have been reported as a molecular biomarker in infectious diseases, such as miRNA-150 and miRNA-146b-5p in human immunodeficiency virus (HIV); miRNA-122, miRNA-21, and miRNA-34a in hepatitis; miRNA-361-5p and miRNA-29c in tuberculosis; miRNA-16 and miRNA-451 in malaria and miRNA-181 in Helicobacter pylori infection. The diagnosis of infection with the help of a biomarker is a non-invasive tool that has shown to have a key role in early diagnosis of infection. The discovery of circulating miRNA in the blood of infected patients has the potential to become a powerful non-invasive biomarker in coming future.

Carrier transport in high mobility InAs nanowire junctionless transistors.

The ability to understand and model the performance limits of nanowire transistors is the key to the design of next generation devices. Here, we report studies on high-mobility junctionless gate-all-around nanowire field effect transistor with carrier mobility reaching 2000 cm(2)/V·s at room temperature. Temperature-dependent transport measurements reveal activated transport at low temperatures due to surface donors, while at room temperature the transport shows a diffusive behavior. From the conductivity data, the extracted value of sound velocity in InAs nanowires is found to be an order less than the bulk. This low sound velocity is attributed to the extended crystal defects that ubiquitously appear in these nanowires. Analyzing the temperature-dependent mobility data, we identify the key scattering mechanisms limiting the carrier transport in these nanowires. Finally, using these scattering models, we perform drift-diffusion based transport simulations of a nanowire field-effect transistor and compare the device performances with experimental measurements. Our device modeling provides insight into performance limits of InAs nanowire transistors and can be used as a predictive methodology for nanowire-based integrated circuits.