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      A Web Resource for Designing Subunit Vaccine Against Major Pathogenic Species of Bacteria

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          Abstract

          Evolution has led to the expansion of survival strategies in pathogens including bacteria and emergence of drug resistant strains proved to be a major global threat. Vaccination is a promising strategy to protect human population. Reverse vaccinology is a more robust vaccine development approach especially with the availability of large-scale sequencing data and rapidly dropping cost of the techniques for acquiring such data from various organisms. The present study implements an immunoinformatic approach for screening the possible antigenic proteins among various pathogenic bacteria to systemically arrive at epitope-based vaccine candidates against 14 pathogenic bacteria. Thousand four hundred and fifty nine virulence factors and Five hundred and forty six products of essential genes were appraised as target proteins to predict potential epitopes with potential to stimulate different arms of the immune system. To address the self-tolerance, self-epitopes were identified by mapping on 1000 human proteome and were removed. Our analysis revealed that 21proteins from 5 bacterial species were found as virulent as well as essential to their survival, proved to be most suitable vaccine target against these species. In addition to the prediction of MHC-II binders, B cell and T cell epitopes as well as adjuvants individually from proteins of all 14 bacterial species, a stringent criteria lead us to identify 252 unique epitopes, which are predicted to be T-cell epitopes, B-cell epitopes, MHC II binders and Vaccine Adjuvants. In order to provide service to scientific community, we developed a web server VacTarBac for designing of vaccines against above species of bacteria. This platform integrates a number of tools that includes visualization tools to present antigenicity/epitopes density on an antigenic sequence. These tools will help users to identify most promiscuous vaccine candidates in a pathogenic antigen. This server VacTarBac is available from URL ( http://webs.iiitd.edu.in/raghava/vactarbac/).

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          Most cited references36

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          DEG 10, an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements

          The combination of high-density transposon-mediated mutagenesis and high-throughput sequencing has led to significant advancements in research on essential genes, resulting in a dramatic increase in the number of identified prokaryotic essential genes under diverse conditions and a revised essential-gene concept that includes all essential genomic elements, rather than focusing on protein-coding genes only. DEG 10, a new release of the Database of Essential Genes (available at http://www.essentialgene.org), has been developed to accommodate these quantitative and qualitative advancements. In addition to increasing the number of bacterial and archaeal essential genes determined by genome-wide gene essentiality screens, DEG 10 also harbors essential noncoding RNAs, promoters, regulatory sequences and replication origins. These essential genomic elements are determined not only in vitro, but also in vivo, under diverse conditions including those for survival, pathogenesis and antibiotic resistance. We have developed customizable BLAST tools that allow users to perform species- and experiment-specific BLAST searches for a single gene, a list of genes, annotated or unannotated genomes. Therefore, DEG 10 includes essential genomic elements under different conditions in three domains of life, with customizable BLAST tools.
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            The success and failure of BCG - implications for a novel tuberculosis vaccine.

            Over the past 50 years, the Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has maintained its position as the world's most widely used vaccine, despite showing highly variable efficacy (0-80%) in different trials. The efficacy of BCG in adults is particularly poor in tropical and subtropical regions. Studies in animal models of TB, supported by data from clinical BCG trials in humans, indicate that this failure is related to pre-existing immune responses to antigens that are common to environmental mycobacteria and Mycobacterium tuberculosis. Here, we discuss the potential mechanisms behind the variation of BCG efficacy and their implications for an improved TB vaccination strategy.
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              A review of antimicrobial peptides and their therapeutic potential as anti-infective drugs.

              Antimicrobial peptides (AMPs) are an essential part of innate immunity that evolved in most living organisms over 2.6 billion years to combat microbial challenge. These small cationic peptides are multifunctional as effectors of innate immunity on skin and mucosal surfaces and have demonstrated direct antimicrobial activity against various bacteria, viruses, fungi, and parasites. This review summarizes their progress to date as commercial antimicrobial drugs for topical and systemic indications. Literature review. Despite numerous clinical trials, no modified AMP has obtained Food & Drug Administration approval yet for any topical or systemic medical indications. While AMPs are recognized as essential components of natural host innate immunity against microbial challenge, their usefulness as a new class of antimicrobial drugs still remains to be proven.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                02 October 2018
                2018
                : 9
                : 2280
                Affiliations
                [1] 1Bioinformatics Centre, CSIR-Institute of Microbial Technology , Chandigarh, India
                [2] 2Centre for Bioinformatics, Computational and Systems Biology, Pathfinder Research and Training Foundation , Greater Noida, India
                [3] 3Center for Computational Biology, Indraprastha Institute of Information Technology , Okhla, India
                Author notes

                Edited by: Pedro A. Reche, Complutense University of Madrid, Spain

                Reviewed by: Giampiero Pietrocola, University of Pavia, Italy; Ghita Ghislat, INSERM U1104 Centre d'immunologie de Marseille-Luminy, France

                *Correspondence: Gajendra P. S. Raghava raghava@ 123456iiitd.ac.in

                This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2018.02280
                6190870
                30356876
                54683886-1734-4d0c-a84d-052196753650
                Copyright © 2018 Nagpal, Usmani and Raghava.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 June 2018
                : 13 September 2018
                Page count
                Figures: 4, Tables: 4, Equations: 0, References: 46, Pages: 11, Words: 6342
                Categories
                Immunology
                Original Research

                Immunology
                reverse vaccinology,vaccine designing,immunotherapeutic,epitopes,antigen,virulence factor,essential genes

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