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Context: Marburg virus (MARV) is a member of the Filoviridae family and causes Marburg virus disease (MVD) among humans and primates. With fatality rates going up to 88%, there is currently no commercialized cure or vaccine to combat the infection. The National Institute of Allergy and Infectious Diseases (NIAID) classified MARV as priority pathogen A, which presages the need for a vaccine candidate which can provide stable, long-term adaptive immunity. The surface glycoprotein (GP) and fusion protein (FP) mediate the adherence, fusion, and entry of the virus into the host cell via the TIM-I receptor. Being important antigenic determinants, studies reveal that GP and FP are prone to evolutionary mutations, underscoring the requirement of a vaccine construct capable of eliciting a robust and sustained immune response. In this computational study, a reverse vaccinology approach was employed to design a combinatorial vaccine from conserved and antigenic epitopes of essential viral proteins of MARV, namely GP, VP24, VP30, VP35, and VP40 along with an endogenous protein large polymerase (L).
Methods: Epitopes for T-cell and B-cell were predicted using TepiTool and ElliPro, respectively. The surface-exposed TLRs like TLR2, TLR4, and TLR5 were used to screen high-binding affinity epitopes using the protein-peptide docking platform MdockPeP. The best binding epitopes were selected and assembled with linkers to design a recombinant multi-epitope vaccine construct which was then modeled in Robetta. The in silico biophysical and biochemical analyses of the recombinant vaccine were performed. The docking and MD simulation of the vaccine using WebGro and CABS-Flex against TLRs support the stable binding of vaccine candidates. A virtual immune simulation to check the immediate and long-term immunogenicity was carried out using the C-ImmSim server.
Results: The biochemical characteristics and docking studies with MD simulation establish the recombinant protein vaccine construct MarVax as a stable, antigenic, and potent vaccine molecule. Immune simulation studies reveal 1-year passive immunity which needs to be validated by in vivo studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681968 | PMC |
http://dx.doi.org/10.1186/s43141-023-00575-w | DOI Listing |
Background: TPM3 (tropomyosin 3) is an actin-binding protein in vascular smooth muscle cells, where posttranslational modifications critically regulate its actin affinity, influencing cardiovascular function. Emerging evidence suggests that Khib (2-hydroxyisobutyrylation) plays a significant role in the cardiovascular system. Histone deacetylase 3 (HDAC3) serves as an "eraser" of Khib marks.
View Article and Find Full Text PDFFoodborne Pathog Dis
December 2024
College of Veterinary Medicine, Jilin Agricultural University, Changchun, China.
Trichinellosis, a zoonotic disease transmitted through food and caused by , is a significant health concern worldwide. Therefore, developing a safe and effective vaccine to combat infection is essential. In this study, a nonantibiotic strain lacking the gene served as a live bacterial vector to deliver antigens to the host, creating a novel oral vaccine.
View Article and Find Full Text PDFMechanobiol Med
December 2024
Department of Biomedical Engineering, College of Engineering and Applied Sciences, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5280, USA.
Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using or strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive.
View Article and Find Full Text PDFIn Silico Pharmacol
December 2024
Laboratory of Chemoinformatics, Infochemistry Scientific Center, ITMO University, Saint Petersburg, Russian Federation.
Unlabelled: Urinary tract infections (UTIs), largely caused by uropathogenic (UPEC), are increasingly resistant to antibiotics and frequently recur. Using immunoinformatics, we designed a multiepitope peptide vaccine targeting UPEC virulence factors, including iron acquisition systems and adhesins. The construct features 12 cytotoxic T lymphocyte epitopes, six helper T lymphocyte epitopes, and six B-cell epitopes,and isoptimized for high antigenicity, immunogenicity, nontoxic, and low allergenic potential.
View Article and Find Full Text PDFFront Public Health
December 2024
School of Business Administration, Shenyang Pharmaceutical University, Shenyang, China.
Background: With the introduction of the accelerated drug review policy in China, the clinical research and development time and the review and approval time of drugs have been shortened accordingly. Especially under the influence of the COVID-19 pandemic, the vaccine formulations released through the accelerated review policy are springing up, and the question of how the accelerated review policy affects the investment portfolio of vaccine enterprises has also attracted more and more attention.
Aims And Methods: The article uses mixed-integer linear programming to develop a new model on portfolio planning for vaccine companies based on the accelerated review policy context.
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