{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:22:54Z","timestamp":1790893374274,"version":"4.1.0"},"reference-count":120,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Antibiotic resistance (AR) is the result of microbes\u2019 natural evolution to withstand the action of antibiotics used against them. AR is rising to a high level across the globe, and novel resistant strains are emerging and spreading very fast. Acinetobacter baumannii is a multidrug resistant Gram-negative bacteria, responsible for causing severe nosocomial infections that are treated with several broad spectrum antibiotics: carbapenems, \u03b2-lactam, aminoglycosides, tetracycline, gentamicin, impanel, piperacillin, and amikacin. The A. baumannii genome is superplastic to acquire new resistant mechanisms and, as there is no vaccine in the development process for this pathogen, the situation is more worrisome. This study was conducted to identify protective antigens from the core genome of the pathogen. Genomic data of fully sequenced strains of A. baumannii were retrieved from the national center for biotechnological information (NCBI) database and subjected to various genomics, immunoinformatics, proteomics, and biophysical analyses to identify potential vaccine antigens against A. baumannii. By doing so, four outer membrane proteins were prioritized: TonB-dependent siderphore receptor, OmpA family protein, type IV pilus biogenesis stability protein, and OprD family outer membrane porin. Immuoinformatics predicted B-cell and T-cell epitopes from all four proteins. The antigenic epitopes were linked to design a multi-epitopes vaccine construct using GPGPG linkers and adjuvant cholera toxin B subunit to boost the immune responses. A 3D model of the vaccine construct was built, loop refined, and considered for extensive error examination. Disulfide engineering was performed for the stability of the vaccine construct. Blind docking of the vaccine was conducted with host MHC-I, MHC-II, and toll-like receptors 4 (TLR-4) molecules. Molecular dynamic simulation was carried out to understand the vaccine-receptors dynamics and binding stability, as well as to evaluate the presentation of epitopes to the host immune system. Binding energies estimation was achieved to understand intermolecular interaction energies and validate docking and simulation studies. The results suggested that the designed vaccine construct has high potential to induce protective host immune responses and can be a good vaccine candidate for experimental in vivo and in vitro studies.<\/jats:p>","DOI":"10.3390\/ijerph19095568","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T08:21:25Z","timestamp":1651652485000},"page":"5568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Vaccinomics to Design a Multi-Epitopes Vaccine for Acinetobacter baumannii"],"prefix":"10.3390","volume":"19","author":[{"given":"Miraj","family":"ud-din","sequence":"first","affiliation":[{"name":"Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-5340","authenticated-orcid":false,"given":"Aqel","family":"Albutti","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, College of Applied Medical Sciences, Qassim University, Buraydah 52571, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0312-5592","authenticated-orcid":false,"given":"Asad","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8793-2972","authenticated-orcid":false,"given":"Saba","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, National University of Medical Sciences, Rawalpindi 46000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0754-1742","authenticated-orcid":false,"given":"Sajjad","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6514-5417","authenticated-orcid":false,"given":"Anam","family":"Naz","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore 54590, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8375-8532","authenticated-orcid":false,"given":"Muhammad","family":"Khurram","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Abasyn University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboob ul","family":"Haq","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Abasyn University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zobia","family":"Afsheen","sequence":"additional","affiliation":[{"name":"Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5759-6568","authenticated-orcid":false,"given":"Youness El","family":"Bakri","sequence":"additional","affiliation":[{"name":"Department of Theoretical and Applied Chemistry, South Ural State University, Lenin Prospect 76, 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Salman","sequence":"additional","affiliation":[{"name":"Department of Health and Biological Sciences, Abasyn University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal","family":"Shaker","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Chung-Ang University, Seoul 06974, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-4250","authenticated-orcid":false,"given":"Muhammad","family":"Tahir ul Qamar","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad 38000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.arcmed.2005.06.009","article-title":"Resistance to antibiotics: Are we in the post-antibiotic era?","volume":"36","author":"Alanis","year":"2005","journal-title":"Arch. Med. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4103\/jgid.jgid_110_18","article-title":"Global contributors to antibiotic resistance","volume":"11","author":"Chokshi","year":"2019","journal-title":"J. Glob. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kulik, E.M., Thurnheer, T., Karygianni, L., Walter, C., Sculean, A., and Eick, S. (2019). Antibiotic susceptibility patterns of aggregatibacter actinomycetemcomitans and porphyromonas gingivalis strains from different decades. Antibiotics, 8.","DOI":"10.3390\/antibiotics8040253"},{"key":"ref_4","unstructured":"PCAST (2015). National Action Plan for Combatting Antibiotic-Resistant Bacteria."},{"key":"ref_5","first-page":"344","article-title":"The antibiotic resistance crisis: Part 2: Management strategies and new agents","volume":"40","author":"Ventola","year":"2015","journal-title":"Pharm. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.addr.2014.10.027","article-title":"Therapeutic strategies to combat antibiotic resistance","volume":"78","author":"Brooks","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Annunziato, G. (2019). Strategies to Overcome Antimicrobial Resistance (AMR) Making Use of Non-Essential Target Inhibitors: A Review. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235844"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1615\/CritRevEukaryotGeneExpr.2014008034","article-title":"Signal Molecule-Dependent Quorum-Sensing and Quorum-Quenching Enzymes in Bacteria","volume":"24","author":"Yanfen","year":"2014","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1242\/jeb.001370","article-title":"Advanced Sequencing Technologies and Their Wider Impact in Microbiology","volume":"210","author":"Hall","year":"2007","journal-title":"J. Exp. Biol."},{"key":"ref_10","first-page":"47","article-title":"In Vitro Activity of Aminoglycosides, Lactam-Lactamases Inhibitor Combinations and Tetracyclines against Multi-Drug Resistant Acinetobacter Baumannii, Isolated from a Tertiary Care Hospital","volume":"2","author":"Afreenish","year":"2010","journal-title":"J. Microbiol. Antimicrob."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1097\/CCM.0000000000004371","article-title":"Key Takeaways from the US CDC\u2019s 2019 Antibiotic Resistance Threats Report for Frontline Providers","volume":"48","author":"Kadri","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nature05446","article-title":"Reducing the Global Burden of Tuberculosis: The Contribution of Improved Diagnostics","volume":"444","author":"Emmett","year":"2006","journal-title":"Nature"},{"key":"ref_13","first-page":"561","article-title":"Antibiotic Resistance Crisis","volume":"40","author":"Mobarki","year":"2019","journal-title":"Int. J. Med. Dev. Ctries"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.drudis.2020.11.036","article-title":"Fighting AMR with Host Immune Response Technology","volume":"26","author":"Oved","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_15","unstructured":"(2022, April 21). ProtParam. Available online: https:\/\/bio.tools\/protparam."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3390\/jox11040013","article-title":"Review on Multiple Facets of Drug Resistance: A Rising Challenge in the 21st Century","volume":"11","author":"Mousumi","year":"2021","journal-title":"J. Xenobiotics"},{"key":"ref_17","unstructured":"Taylor, D. (2022, April 22). The Pharmaceutical Industry and the Future of Drug Development. Available online: https:\/\/pubs.rsc.org\/en\/content\/chapterhtml\/2015\/bk9781782621898-00001?isbn=978-1-78262-189-8."},{"key":"ref_18","unstructured":"Lantian, Z., Zhang, Y., Ge, Y., Zhu, X., and Pan, J. (2020). Regulatory Mechanisms and Promising Applications of Quorum Sensing-Inhibiting Agents in Control of Bacterial Biofilm Formation. Front. Microbiol., 2558."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.2147\/IDR.S173867","article-title":"Antibiotic resistance: A rundown of a global crisis","volume":"11","author":"Aslam","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20162562","DOI":"10.1098\/rspb.2016.2562","article-title":"Why does drug resistance readily evolve but vaccine resistance does not?","volume":"284","author":"Kennedy","year":"2017","journal-title":"Proc. R. Soc. B Biol. Sci."},{"key":"ref_21","unstructured":"Goldsby, R.A., Kindt, T.J., Osborne, B.A., and Kuby, J. (2003). Chapter 2: Cells and Organs of the Immune System. Immunology, W. H. Freeman and Company. [5th ed.]. Available online: https:\/\/www.scirp.org\/(S(351jmbntvnsjt1aadkposzje))\/reference\/ReferencesPapers.aspx?ReferenceID=1913594."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12283","DOI":"10.1073\/pnas.1400472111","article-title":"History of vaccination","volume":"111","author":"Plotkin","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"184","DOI":"10.4161\/hv.4.3.6313","article-title":"Genome-based vaccine development: A short cut for the future","volume":"4","author":"Moriel","year":"2008","journal-title":"Hum. Vaccines"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.biologicals.2017.08.004","article-title":"Towards a peptide-based vaccine against Shigella sonnei: A subtractive reverse vaccinology based approach","volume":"50","author":"Baseer","year":"2017","journal-title":"Biologicals"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1086\/529198","article-title":"Acinetobacter baumannii: Epidemiology, antimicrobial resistance, and treatment options","volume":"46","author":"Eliopoulos","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gellings, P.S., Wilkins, A.A., and Morici, L.A. (2020). Recent Advances in the Pursuit of an Effective Acinetobacter baumannii Vaccine. Pathogens, 9.","DOI":"10.3390\/pathogens9121066"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"24373","DOI":"10.1038\/srep24373","article-title":"BPGA-an ultra-fast pan-genome analysis pipeline","volume":"6","author":"Chaudhari","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.genrep.2017.04.008","article-title":"Identification of plausible drug targets by investigating the druggable genome of MDR Staphylococcus epidermidis","volume":"7","author":"Sanober","year":"2017","journal-title":"Gene Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.meegid.2015.03.027","article-title":"Identification of putative vaccine candidates against Helicobacter pylori exploiting exoproteome and secretome: A reverse vaccinology based approach","volume":"32","author":"Naz","year":"2015","journal-title":"Infect. Genet. Evol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kumar Jaiswal, A., Tiwari, S., Jamal, S.B., Barh, D., Azevedo, V., and Soares, S.C. (2017). An in silico identification of common putative vaccine candidates against treponema pallidum: A reverse vaccinology and subtractive genomics based approach. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18020402"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4476","DOI":"10.1038\/s41598-019-40940-9","article-title":"\u2018Genome skimming\u2019 with the MinION hand-held sequencer identifies CITES-listed shark species in India\u2019s exports market","volume":"9","author":"Johri","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.meegid.2011.10.017","article-title":"Mycoplasma genitalium: A comparative genomics study of metabolic pathways for the identification of drug and vaccine targets","volume":"12","author":"Butt","year":"2012","journal-title":"Infect. Genet. Evol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"234","DOI":"10.6026\/97320630005234","article-title":"Protein sequence redundancy reduction: Comparison of various method","volume":"5","author":"Sikic","year":"2010","journal-title":"Bioinformation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1093\/bioinformatics\/btl158","article-title":"Cd-hit: A fast program for clustering and comparing large sets of protein or nucleotide sequences","volume":"22","author":"Li","year":"2006","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rizwan, M., Naz, A., Ahmad, J., Naz, K., Obaid, A., Parveen, T., Ahsan, M., and Ali, A. (2017). VacSol: A high throughput in silico pipeline to predict potential therapeutic targets in prokaryotic pathogens using subtractive reverse vaccinology. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1540-0"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ygeno.2014.07.007","article-title":"An insight into the exploration of druggable genome of Streptococcus gordonii for the identification of novel therapeutic candidates","volume":"104","author":"Azam","year":"2014","journal-title":"Genomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2019.02.023","article-title":"Combating tigecycline resistant Acinetobacter baumannii: A leap forward towards multi-epitope based vaccine discovery","volume":"132","author":"Ahmad","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hara, Y., Mohamed, R., and Nathan, S. (2009). Immunogenic Burkholderia pseudomallei outer membrane proteins as potential candidate vaccine targets. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006496"},{"key":"ref_39","first-page":"7","article-title":"Gram-negative outer membrane vesicles in vaccine development","volume":"12","author":"Collins","year":"2011","journal-title":"Discov. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ygeno.2017.05.001","article-title":"Prediction of vaccine candidates against Pseudomonas aeruginosa: An integrated genomics and proteomics approach","volume":"109","author":"Rashid","year":"2017","journal-title":"Genomics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D325","DOI":"10.1093\/nar\/gki008","article-title":"VFDB: A reference database for bacterial virulence factors","volume":"33","author":"Chen","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1111\/j.1365-3083.2008.02107.x","article-title":"Developing antibacterial vaccines in genomics and proteomics era","volume":"67","author":"Kaushik","year":"2008","journal-title":"Scand. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1080\/07391102.2019.1692072","article-title":"Proteome-wide screening for designing a multi-epitope vaccine against emerging pathogen Elizabethkingia anophelis using immunoinformatic approaches","volume":"38","author":"Nain","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_44","unstructured":"(2022, April 22). ExPASy. Available online: https:\/\/www.expasy.org\/."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/protein\/4.2.155","article-title":"Correlation between stability of a protein and its dipeptide composition: A novel approach for predicting in vivo stability of a protein from its primary sequence","volume":"4","author":"Guruprasad","year":"1990","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/bioinformatics\/17.9.849","article-title":"The HMMTOP transmembrane topology prediction server","volume":"17","author":"Tusnady","year":"2001","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Doytchinova, I.A., and Flower, D.R. (2007). VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-4"},{"key":"ref_48","first-page":"16","article-title":"SPAAN: A software for prediction of adhesins and adhesin-like proteins using neural networks","volume":"16","author":"Sachdeva","year":"2004","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.micpath.2017.12.063","article-title":"Subtractive genome analysis for in silico identification and characterization of novel drug targets in Streptococcus pneumonia strain JJA","volume":"115","author":"Wadood","year":"2018","journal-title":"Microb. Pathog."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"297505","DOI":"10.1155\/2010\/297505","article-title":"Vaxign: The first web-based vaccine design program for reverse vaccinology and applications for vaccine development","volume":"2010","author":"He","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"139580","DOI":"10.1155\/2015\/139580","article-title":"Pan-Genome analysis of human gastric pathogen H. pylori: Comparative genomics and pathogenomics approaches to identify regions associated with pathogenicity and prediction of potential core therapeutic targets","volume":"2015","author":"Ali","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Naz, K., Naz, A., Ashraf, S.T., Rizwan, M., Ahmad, J., Baumbach, J., and Ali, A. (2019). PanRV: Pangenome-reverse vaccinology approach for identifications of potential vaccine candidates in microbial pangenome. BMC Bioinform., 20.","DOI":"10.1186\/s12859-019-2713-9"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hassan, A., Naz, A., Obaid, A., Paracha, R.Z., Naz, K., Awan, F.M., Muhmmad, S.A., Janjua, H.A., Ahmad, J., and Ali, A. (2016). Pangenome and immuno-proteomics analysis of Acinetobacter baumannii strains revealed the core peptide vaccine targets. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2951-4"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D405","DOI":"10.1093\/nar\/gku938","article-title":"The immune epitope database (IEDB) 3.0","volume":"43","author":"Vita","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_55","unstructured":"Janeway, C.A., Travers, P., Walport, M., and Shlomchik, M.J. (2001). The major histocompatibility complex and its functions. Immunobiology: The Immune System in Health and Disease, Garland Science. [5th ed.]."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Garg, A., and Gupta, D. (2008). VirulentPred: A SVM based prediction method for virulent proteins in bacterial pathogens. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-62"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dimitrov, I., Flower, D.R., and Doytchinova, I. (2013). AllerTOP-a server for in silico prediction of allergens. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-S6-S4"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3390\/vaccines2030515","article-title":"Peptide vaccine: Progress and challenges","volume":"2","author":"Li","year":"2014","journal-title":"Vaccines"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1039\/C5SC03892H","article-title":"Peptide-based synthetic vaccines","volume":"7","author":"Skwarczynski","year":"2016","journal-title":"Chem. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"974","DOI":"10.3390\/toxins7030974","article-title":"Cholera Toxin B: One Subunit with Many Pharmaceutical Applications","volume":"7","author":"Baldauf","year":"2015","journal-title":"Toxins"},{"key":"ref_61","unstructured":"ProtParam, K.E. (2022, April 01). ExPASy-ProtParam Tool. Available online: https:\/\/web.expasy.org\/protparam\/."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W72","DOI":"10.1093\/nar\/gki396","article-title":"SCRATCH: A protein structure and structural feature prediction server","volume":"33","author":"Cheng","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1101\/gr.4086505","article-title":"Galaxy: A platform for interactive large-scale genome analysis","volume":"15","author":"Giardine","year":"2005","journal-title":"Genome Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"W384","DOI":"10.1093\/nar\/gkt458","article-title":"GalaxyRefine: Protein structure refinement driven by side-chain repacking","volume":"41","author":"Heo","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Craig, D.B., and Dombkowski, A.A. (2013). Disulfide by Design 2.0: A web-based tool for disulfide engineering in proteins. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-346"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"W526","DOI":"10.1093\/nar\/gki376","article-title":"JCat: A novel tool to adapt codon usage of a target gene to its potential expression host","volume":"33","author":"Grote","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_67","unstructured":"Rapin, N., Lund, O., and Castiglione, F. (2022, April 22). C-Immsim 10.1 Server. Available online: https:\/\/www.iac.cnr.it\/~filippo\/projects\/c-immsim-online.html."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Rapin, N., Lund, O., Bernaschi, M., and Castiglione, F. (2010). Computational immunology meets bioinformatics: The use of prediction tools for molecular binding in the simulation of the immune system. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009862"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Morris, G.M., and Lim-Wilby, M. (2008). Molecular docking. Molecular Modeling of Proteins, Springer.","DOI":"10.1007\/978-1-59745-177-2_19"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5240","DOI":"10.1038\/s41598-019-41496-4","article-title":"Prioritization of potential vaccine targets using comparative proteomics and designing of the chimeric multi-epitope vaccine against Pseudomonas aeruginosa","volume":"9","author":"Solanki","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"40611","DOI":"10.1074\/jbc.M112.404608","article-title":"Structural analyses of human Toll-like receptor 4 polymorphisms D299G and T399I","volume":"287","author":"Ohto","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"W363","DOI":"10.1093\/nar\/gki481","article-title":"PatchDock and SymmDock: Servers for rigid and symmetric docking","volume":"33","author":"Inbar","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/prot.21495","article-title":"FireDock: Fast interaction refinement in molecular docking","volume":"69","author":"Andrusier","year":"2007","journal-title":"Proteins Struct. Funct. Bioinforma."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"79651","DOI":"10.1039\/C6RA19162B","article-title":"A one-pot multicomponent facile synthesis of dihydropyrimidin-2(1: H)-thione derivatives using triphenylgermane as a catalyst and its binding pattern validation","volume":"6","author":"Andleeb","year":"2016","journal-title":"RSC Adv."},{"key":"ref_76","unstructured":"Case, D.A., Cerutti, D.S., Cheateham, T.E., Darden, T.A., Duke, R.E., Giese, T.J., Gohlke, H., Goetz, A.W., Greene, D., and Homeyer, N. (2022, April 22). AMBER16 Package, University of California, San Francisco. Available online: https:\/\/ambermd.org\/doc12\/Amber16.pdf."},{"key":"ref_77","first-page":"U403","article-title":"Antechamber: An accessory software package for molecular mechanical calculations","volume":"222","author":"Wang","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4208\/cicp.210711.121011s","article-title":"Examining electrostatic influences on base-flipping: A comparison of TIP3P and GB solvent models","volume":"13","author":"Brice","year":"2013","journal-title":"Commun. Comput. Phys."},{"key":"ref_79","unstructured":"Kerrigan, J.E. (2022, April 01). AMBER 10.0 Introductory Tutorial. Available online: https:\/\/ambermd.org\/."},{"key":"ref_80","first-page":"29","article-title":"The FF14SB force field","volume":"14","author":"Case","year":"2014","journal-title":"Amber"},{"key":"ref_81","unstructured":"Lavenda, B.H. (2016). Statistical Physics: A Probabilistic Approach, Courier Dover Publications."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/jcc.20290","article-title":"The Amber biomolecular simulation programs","volume":"26","author":"Case","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1063\/1.470648","article-title":"Constant pressure molecular dynamics simulation: The Langevin piston method","volume":"103","author":"Feller","year":"1995","journal-title":"J. Chem. Phys."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/08927029408021981","article-title":"On the Berendsen thermostat","volume":"13","author":"Lemak","year":"1994","journal-title":"Mol. Simul."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.py: An efficient program for end-state free energy calculations","volume":"8","author":"Miller","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e20046","DOI":"10.1002\/tpg2.20046","article-title":"Pan-genome: A promising resource for noncoding RNA discovery in plants","volume":"13","author":"Zhu","year":"2020","journal-title":"Plant Genome"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4156","DOI":"10.1093\/bioinformatics\/btz168","article-title":"ppsPCP: A plant presence\/absence variants scanner and pan-genome construction pipeline","volume":"35","author":"Zhu","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.gene.2019.03.049","article-title":"Prediction of new vaccine targets in the core genome of Corynebacterium pseudotuberculosis through omics approaches and reverse vaccinology","volume":"702","author":"Alves","year":"2019","journal-title":"Gene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1093\/bib\/bbx117","article-title":"V Microbial genome analysis: The COG approach","volume":"20","author":"Galperin","year":"2019","journal-title":"Brief. Bioinform."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1080\/14760584.2020.1794832","article-title":"An overview of in silico vaccine design against different pathogens and cancer","volume":"19","author":"Kardani","year":"2020","journal-title":"Expert Rev. Vaccines"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3524","DOI":"10.1080\/07391102.2018.1519460","article-title":"Vaccinomics approach for developing multi-epitope peptide pneumococcal vaccine","volume":"37","author":"Dorosti","year":"2019","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3389\/fpubh.2018.00062","article-title":"Vaccines meet big data: State-ofthe- Art and future prospects. From the classical 3is (\u201cisolate-inactivate-inject\u201d) vaccinology 1.0 to vaccinology 3.0, vaccinomics, and Beyond: A historical overview","volume":"6","author":"Bragazzi","year":"2018","journal-title":"Front. Public Health"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1126\/science.1152622","article-title":"Toward an AIDS vaccine","volume":"320","author":"Walker","year":"2008","journal-title":"Science"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1177\/1352458517707069","article-title":"Dimethyl fumarate induces changes in B-and T-lymphocyte function independent of the effects on absolute lymphocyte count","volume":"24","author":"Longbrake","year":"2018","journal-title":"Mult. Scler. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.micpath.2019.05.010","article-title":"Conserved B and T cell epitopes prediction of ebola virus glycoprotein for vaccine development: An immuno-informatics approach","volume":"132","author":"Ahmad","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"vez002","DOI":"10.1093\/ve\/vez002.024","article-title":"A25 Impact of polymorphism in the hepatitis B surface gene on human leukocyte antigen (HLA) class II","volume":"5","author":"Choga","year":"2019","journal-title":"Virus Evol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"104389","DOI":"10.1016\/j.compbiomed.2021.104389","article-title":"Designing multi-epitope vaccine against Staphylococcus aureus by employing subtractive proteomics, reverse vaccinology and immuno-informatics approaches","volume":"132","author":"Ahmad","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s12967-018-1672-7","article-title":"Peptide vaccine against chikungunya virus: Immuno-informatics combined with molecular docking approach","volume":"16","author":"Bari","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Ullah, A., Ahmad, S., Ismail, S., Afsheen, Z., Khurram, M., Tahir ul Qamar, M., AlSuhaymi, N., Alsugoor, M.H., and Allemailem, K.S. (2021). Towards A Novel Multi-Epitopes Chimeric Vaccine for Simulating Strong Immune Responses and Protection against Morganella morganii. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph182010961"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"105120","DOI":"10.1016\/j.meegid.2021.105120","article-title":"Identification of immunodominant epitopes in allelic variants VK210 and VK247 of Plasmodium Vivax Circumsporozoite immunogen","volume":"96","author":"Naz","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"105151","DOI":"10.1016\/j.compbiomed.2021.105151","article-title":"Designing of a multi-epitopes-based peptide vaccine against rift valley fever virus and its validation through integrated computational approaches","volume":"141","author":"Fatima","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.humimm.2020.05.010","article-title":"Computational design of a novel multi-epitope vaccine against Coxiella burnetii","volume":"81","author":"Jaydari","year":"2020","journal-title":"Hum. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1126\/science.aax3879","article-title":"The evolution of antibiotic resistance","volume":"365","author":"MacLean","year":"2019","journal-title":"Science"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1128\/CMR.00058-07","article-title":"Acinetobacter baumannii: Emergence of a successful pathogen","volume":"21","author":"Peleg","year":"2008","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/nrmicro1789","article-title":"An increasing threat in hospitals: Multidrug-Resistant Acinetobacter baumannii","volume":"5","author":"Dijkshoorn","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Wareth, G., Brandt, C., Sprague, L.D., Neubauer, H., and Pletz, M.W. (2020). Spatio-temporal distribution of Acinetobacter baumannii in Germany\u2014A comprehensive systematic review of studies on resistance development in humans (2000\u20132018). Microorganisms, 8.","DOI":"10.3390\/microorganisms8030375"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.drudis.2008.12.007","article-title":"The use of genomics in microbial vaccine development","volume":"14","author":"Bambini","year":"2009","journal-title":"Drug Discov. Today"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Bidmos, F.A., Siris, S., Gladstone, C.A., and Langford, P.R. (2018). Bacterial Vaccine Antigen Discovery in the Reverse Vaccinology 2.0 Era: Progress and Challenges. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02315"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1359-6446(03)02689-8","article-title":"Reverse vaccinology","volume":"8","author":"Mora","year":"2003","journal-title":"Drug Discov. Today"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0264-410X(02)00566-2","article-title":"Two years into reverse vaccinology","volume":"21","author":"Capecchi","year":"2003","journal-title":"Vaccine"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s13353-014-0265-2","article-title":"Overview of computational vaccinology: Vaccine development through information technology","volume":"56","author":"Vaishnav","year":"2015","journal-title":"J. Appl. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"21929","DOI":"10.1038\/s41598-021-01283-6","article-title":"An integrated computational framework to design a multi-epitopes vaccine against Mycobacterium tuberculosis","volume":"11","author":"Albutti","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1126\/science.1109869","article-title":"Identification of a universal Group B streptococcus vaccine by multiple genome screen","volume":"309","author":"Maione","year":"2005","journal-title":"Science"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1007\/s10989-021-10279-9","article-title":"Computational Design of a Multi-epitope Vaccine Against Clostridium chauvoei: An Immunoinformatics Approach","volume":"27","year":"2021","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_117","first-page":"1","article-title":"Reverse vaccinology assisted designing of multiepitope-based subunit vaccine against SARS-CoV-2","volume":"9","author":"Shahid","year":"2020","journal-title":"Infect. Dis. Poverty"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1080\/21645515.2015.1010910","article-title":"Identification of novel vaccine candidates against Acinetobacter baumannii using reverse vaccinology","volume":"11","author":"Chiang","year":"2015","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1038\/s41598-022-06582-0","article-title":"Enhanced antibacterial effect of a novel Friunavirus phage vWU2001 in combination with colistin against carbapenem-resistant Acinetobacter baumannii","volume":"12","author":"Wintachai","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Ayoub Moubareck, C., and Hammoudi Halat, D. (2020). Insights into Acinetobacter baumannii: A review of microbiological, virulence, and resistance traits in a threatening nosocomial pathogen. Antibiotics, 9.","DOI":"10.3390\/antibiotics9030119"}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/9\/5568\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:05:56Z","timestamp":1760137556000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/19\/9\/5568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,4]]},"references-count":120,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijerph19095568"],"URL":"https:\/\/doi.org\/10.3390\/ijerph19095568","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,4]]}}}