Development of a novel multi­epitope vaccine against the pathogenic human polyomavirus V6/7 using reverse vaccinology.

BACKGROUND: Human polyomaviruses contribute to human oncogenesis through persistent infections, but currently there is no effective preventive measure against the malignancies caused by this virus. Therefore, the development of a safe and effective vaccine against HPyV is of high priority. METHODS: First, the proteomes of 2 polyomavirus species (HPyV6 and HPyV7) were downloaded from the NCBI database for the selection of the target proteins. The epitope identification process focused on selecting proteins that were crucial, associated with virulence, present on the surface, antigenic, non-toxic, and non-homologous with the human proteome. Then, the immunoinformatic methods were used to identify cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes from the target antigens, which could be used to create epitope-based vaccine. The physicochemical features of the designed vaccine were predicted through various online servers. The binding pattern and stability between the vaccine candidate and Toll-like receptors were analyzed through molecular docking and molecular dynamics (MD) simulation, while the immunogenicity of the designed vaccines was assessed using immune simulation. RESULTS: Online tools were utilized to forecast the most optimal epitope from the immunogenic targets, including LTAg, VP1, and VP1 antigens of HPyV6 and HPyV7. A multi-epitope vaccine was developed by combining 10 CTL, 7 HTL, and 6 LBL epitopes with suitable linkers and adjuvant. The vaccine displayed 98.35% of the world's population coverage. The 3D model of the vaccine structure revealed that the majority of residues (87.7%) were located in favored regions of the Ramachandran plot. The evaluation of molecular docking and MD simulation revealed that the constructed vaccine exhibits a strong binding (-1414.0 kcal/mol) towards the host's TLR4. Moreover, the vaccine-TLR complexes remained stable throughout the dynamic conditions present in the natural environment. The immune simulation results demonstrated that the vaccine design had the capacity to elicit robust immune responses in the host. CONCLUSION: The multi-parametric analysis revealed that the designed vaccine is capable of inducing sustained immunity against the selected polyomaviruses, although further in-vivo investigations are needed to verify its effectiveness.

Matricaria chamomilla essential oil-loaded hybrid electrospun nanofibers based on polycaprolactone/sulfonated chitosan/ZIF-8 nanoparticles for wound healing acceleration.

Recently, developing antibacterial wound dressings based on biomaterials display good biocompatibility and the potential to accelerate wound healing. For this aim, we prepared eco-friendly and biodegradable nanofibers (NFs) based on N-(3-sulfopropyl)chitosan/ poly (ε-caprolactone) incorporated by zeolite imidazolate framework-8 nanoparticles (ZIF-8 NPs) and chamomile essential oil (MCEO) via the electrospinning technique for their efficacy as wound dressing scaffolds. Fabricated NFs were characterized and studied for their structural, morphological, mechanical, hydrophilic, and thermal stability properties. The results of scanning electron microscopy (SEM) revealed that adding the ZIF-8 NPs/ MCEO, very slightly influenced the average diameter of NFs (PCL/SPCS (90:10) with 90 ± 32 nm). The developed uniform MCEO-loaded ZIF-8/PCL/SPCS NFs displayed better cytocompatibility, proliferation, and physicochemical properties (e.g. thermal stability and mechanical properties) than neat NFs. The results of cytocompatibility, DAPI (4',6-diamidino-2-phenylindole) staining study, and SEM micrographs demonstrated that formulated NFs had promising adhesion and proliferation against normal human foreskin fibroblasts-2 (HFF-2 cell line). The prepared NFs revealed excellent antibacterial activity against both Staphylococcus aureus and Escherichia coli with inhibition of 32.3 mm and 31.2 mm, respectively. Accordingly, the newly developed antibacterial NFs hold great potential as effective biomaterials for use as an active platform in wound healing applications.

Stimulus-Responsive Sequential Release Systems for Drug and Gene Delivery.

In recent years, a range of studies have been conducted with the aim to design and characterize delivery systems that are able to release multiple therapeutic agents in controlled and programmed temporal sequences, or with spatial resolution inside the body. This sequential release occurs in response to different stimuli, including changes in pH, redox potential, enzyme activity, temperature gradients, light irradiation, and by applying external magnetic and electrical fields. Sequential release (SR)-based delivery systems, are often based on a range of different micro- or nanocarriers and may offer a silver bullet in the battle against various diseases, such as cancer. Their distinctive characteristic is the ability to release one or more drugs (or release drugs along with genes) in a controlled sequence at different times or at different sites. This approach can lengthen gene expression periods, reduce the side effects of drugs, enhance the efficacy of drugs, and induce an anti-proliferative effect on cancer cells due to the synergistic effects of genes and drugs. The key objective of this review is to summarize recent progress in SR-based drug/gene delivery systems for cancer and other diseases.