{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:49:48Z","timestamp":1780465788584,"version":"3.54.1"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Manipal Academy of Higher Education, Manipal"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Chlamydia trachomatis<\/jats:italic> (CT) remains a significant infectious cause of blindness and sexually transmitted infections worldwide. The objective and novelty of this study lie in using different serovars of CT to design a broad-spectrum multi-epitope vaccine that might confer immunity against different CT infections. As the major outer membrane protein in CT has good immunodominance properties and high conservation and also determines the several serotypes of CT, it is selected as an antibody target in this study. T-cell and B-cell epitopes from serovars A, B, D, E, L1, and L2 were predicted and combined into a single construct by incorporating adjuvants and linkers to enhance immunogenicity and stability. Physicochemical characterization confirmed the constructed vaccine\u2019s anti-allergic, immunogenicity, and thermostable characteristics, followed by structural modeling to refine its 3D configuration. The 3D model structure of the vaccine was validated through the Ramachandran plot and ProSA z-score. Molecular docking studies of the vaccine demonstrated stable binding with toll-like receptor 3, along with molecular dynamics simulations and binding free energy calculations supporting the complex\u2019s stability. In silico cloning has indicated a high potential for expression in <jats:italic>Escherichia coli<\/jats:italic>. Lastly, immune simulations revealed robust activation of B cells, cytotoxic T cells, and antigen-presenting cells, alongside significant production of IgM, IgG antibodies, and balanced Th1\/Th2 cytokine response, which is crucial for effective immunity. These results suggest the multi-epitope vaccine could effectively induce comprehensive immune responses against CT, highlighting the need for further in vivo validation to advance this promising candidate toward clinical use.<\/jats:p>","DOI":"10.1038\/s41598-024-81736-w","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T12:11:36Z","timestamp":1733141496000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Immunoinformatics design of a multi-epitope vaccine for Chlamydia trachomatis major outer membrane proteins"],"prefix":"10.1038","volume":"14","author":[{"given":"Seema","family":"Shetty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swagatika","family":"Dash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avinash","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashidhar","family":"Vishwanath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvarna G.","family":"Kini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Brand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"81736_CR1","unstructured":"Chlamydia. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/chlamydia."},{"key":"81736_CR2","unstructured":"Trachoma. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/trachoma."},{"key":"81736_CR3","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1016\/j.vaccine.2021.03.043","volume":"39","author":"SM Murray","year":"2021","unstructured":"Murray, S. M. & McKay, P. F. Chlamydia trachomatis: Cell biology, immunology and vaccination. Vaccine 39, 2965\u20132975 (2021).","journal-title":"Vaccine"},{"key":"81736_CR4","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1007\/s42770-021-00533-z","volume":"52","author":"S Shetty","year":"2021","unstructured":"Shetty, S. et al. Diagnosis of Chlamydia trachomatis genital infections in the era of genomic medicine. Braz. J. Microbiol. Publ. Braz. Soc. Microbiol. 52, 1327\u20131339 (2021).","journal-title":"Braz. J. Microbiol. Publ. Braz. Soc. Microbiol."},{"key":"81736_CR5","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1016\/j.cmi.2022.02.013","volume":"28","author":"HJC de Vries","year":"2022","unstructured":"de Vries, H. J. C. et al. Call for consensus in Chlamydia trachomatis nomenclature: moving from biovars, serovars, and serotypes to genovariants and genotypes. Clin. Microbiol. Infect. 28, 761\u2013763 (2022).","journal-title":"Clin. Microbiol. Infect."},{"key":"81736_CR6","doi-asserted-by":"publisher","DOI":"10.5772\/31946","author":"CM Carmen","year":"2012","unstructured":"Carmen, C. M. et al. Host immune response to Chlamydia infection. Chlamydia https:\/\/doi.org\/10.5772\/31946 (2012).","journal-title":"Chlamydia"},{"issue":"25","key":"81736_CR7","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1038\/s41580-024-00729-9","volume":"2024","author":"JM Tsai","year":"2024","unstructured":"Tsai, J. M., Nowak, R. P., Ebert, B. L. & Fischer, E. S. Targeted protein degradation: from mechanisms to clinic. Nat. Rev. Mol. Cell Biol. 2024(25), 740\u2013757 (2024).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"81736_CR8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.fertnstert.2007.05.070","volume":"91","author":"A Malik","year":"2009","unstructured":"Malik, A., Jain, S., Rizvi, M., Shukla, I. & Hakim, S. Chlamydia trachomatis infection in women with secondary infertility. Fertil. Steril. 91, 91\u201395 (2009).","journal-title":"Fertil. Steril."},{"key":"81736_CR9","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1517\/14656566.2015.999041","volume":"16","author":"SA Kohlhoff","year":"2015","unstructured":"Kohlhoff, S. A. & Hammerschlag, M. R. Treatment of chlamydial infections: 2014 update. Expert Opin. Pharmacother. 16, 205\u2013212 (2015).","journal-title":"Expert Opin. Pharmacother."},{"key":"81736_CR10","doi-asserted-by":"publisher","first-page":"656","DOI":"10.2741\/4611","volume":"23","author":"T Mestrovic","year":"2018","unstructured":"Mestrovic, T. & Ljubin-Sternak, S. Molecular mechanisms of Chlamydia trachomatis resistance to antimicrobial drugs. Front. Biosci. Landmark Ed. 23, 656\u2013670 (2018).","journal-title":"Front. Biosci. Landmark Ed."},{"key":"81736_CR11","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1080\/14760584.2021.1899817","volume":"20","author":"LM de la Maza","year":"2021","unstructured":"de la Maza, L. M., Darville, T. L. & Pal, S. Chlamydia vaccines: where are we and how far is there to go?. Expert Rev. Vaccines 20, 421 (2021).","journal-title":"Expert Rev. Vaccines"},{"key":"81736_CR12","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1093\/abbs\/gmu016","volume":"46","author":"J Tu","year":"2014","unstructured":"Tu, J. et al. A multi-epitope vaccine based on Chlamydia trachomatis major outer membrane protein induces specific immunity in mice. Acta Biochim. Biophys. Sin. 46, 401\u2013408 (2014).","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"81736_CR13","doi-asserted-by":"publisher","first-page":"e61139","DOI":"10.1371\/journal.pone.0061139","volume":"8","author":"FO Atanu","year":"2013","unstructured":"Atanu, F. O., Oviedo-Orta, E. & Watson, K. A. A novel transport mechanism for MOMP in Chlamydophila pneumoniae and its putative role in immune-therapy. PloS One 8, e61139 (2013).","journal-title":"PloS One"},{"key":"81736_CR14","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1093\/infdis\/jiv137","volume":"212","author":"AW Olsen","year":"2015","unstructured":"Olsen, A. W., Follmann, F., Erneholm, K., Rosenkrands, I. & Andersen, P. Protection against chlamydia trachomatis infection and upper genital tract pathological changes by vaccine-promoted neutralizing antibodies directed to the VD4 of the major outer membrane protein. J. Infect. Dis. 212, 978\u2013989 (2015).","journal-title":"J. Infect. Dis."},{"key":"81736_CR15","doi-asserted-by":"publisher","first-page":"13","DOI":"10.2147\/ITT.S241064","volume":"9","author":"AN Oli","year":"2020","unstructured":"Oli, A. N. et al. Immunoinformatics and vaccine development: An overview. ImmunoTargets Ther. 9, 13\u201330 (2020).","journal-title":"ImmunoTargets Ther."},{"key":"81736_CR16","doi-asserted-by":"publisher","first-page":"D115","DOI":"10.1093\/nar\/gkh131","volume":"32","author":"R Apweiler","year":"2004","unstructured":"Apweiler, R. et al. UniProt: the Universal Protein knowledgebase. Nucleic Acids Res. 32, D115 (2004).","journal-title":"Nucleic Acids Res."},{"key":"81736_CR17","doi-asserted-by":"publisher","first-page":"2881","DOI":"10.1242\/jcs.186205","volume":"129","author":"NMG Dieckmann","year":"2016","unstructured":"Dieckmann, N. M. G., Frazer, G. L., Asano, Y., Stinchcombe, J. C. & Griffiths, G. M. The cytotoxic T lymphocyte immune synapse at a glance. J. Cell Sci. 129, 2881\u20132886 (2016).","journal-title":"J. Cell Sci."},{"key":"81736_CR18","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1093\/bioinformatics\/btn128","volume":"24","author":"C Lundegaard","year":"2008","unstructured":"Lundegaard, C., Lund, O. & Nielsen, M. Accurate approximation method for prediction of class I MHC affinities for peptides of length 8, 10 and 11 using prediction tools trained on 9mers. Bioinforma. Oxf. Engl. 24, 1397\u20131398 (2008).","journal-title":"Bioinforma. Oxf. Engl."},{"key":"81736_CR19","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1155\/2012\/925135","volume":"2012","author":"RV Luckheeram","year":"2012","unstructured":"Luckheeram, R. V., Zhou, R., Verma, A. D. & Xia, B. CD4+T cells: Differentiation and functions. Clin. Dev. Immunol. 2012, 12 (2012).","journal-title":"Clin. Dev. Immunol."},{"key":"81736_CR20","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1111\/imm.12889","volume":"154","author":"KK Jensen","year":"2018","unstructured":"Jensen, K. K. et al. Improved methods for predicting peptide binding affinity to MHC class II molecules. Immunology 154, 394\u2013406 (2018).","journal-title":"Immunology"},{"key":"81736_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/2680160","volume":"2017","author":"JL Sanchez-Trincado","year":"2017","unstructured":"Sanchez-Trincado, J. L., Gomez-Perosanz, M. & Reche, P. A. Fundamentals and methods for T- and B-cell epitope prediction. J. Immunol. Res. 2017, 1\u201314 (2017).","journal-title":"J. Immunol. Res."},{"key":"81736_CR22","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1002\/prot.21078","volume":"65","author":"S Saha","year":"2006","unstructured":"Saha, S. & Raghava, G. P. S. Prediction of continuous B-cell epitopes in an antigen using recurrent neural network. Proteins 65, 40\u201348 (2006).","journal-title":"Proteins"},{"key":"81736_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.131517","volume":"267","author":"S Ahmad","year":"2024","unstructured":"Ahmad, S. et al. In silico design of a novel multi-epitope vaccine against HCV infection through immunoinformatics approaches. Int. J. Biol. Macromol. 267, 131517 (2024).","journal-title":"Int. J. Biol. Macromol."},{"key":"81736_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-8-4","volume":"8","author":"IA Doytchinova","year":"2007","unstructured":"Doytchinova, I. A. & Flower, D. R. VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinformatics 8, 1\u20137 (2007).","journal-title":"BMC Bioinformatics"},{"key":"81736_CR25","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/j.vaccine.2006.09.032","volume":"25","author":"IA Doytchinova","year":"2007","unstructured":"Doytchinova, I. A. & Flower, D. R. Identifying candidate subunit vaccines using an alignment-independent method based on principal amino acid properties. Vaccine 25, 856\u2013866 (2007).","journal-title":"Vaccine"},{"key":"81736_CR26","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1093\/bioinformatics\/btt619","volume":"30","author":"I Dimitrov","year":"2014","unstructured":"Dimitrov, I., Naneva, L., Doytchinova, I. & Bangov, I. AllergenFP: Allergenicity prediction by descriptor fingerprints. Bioinformatics 30, 846\u2013851 (2014).","journal-title":"Bioinformatics"},{"key":"81736_CR27","doi-asserted-by":"crossref","unstructured":"Gupta, S. et al. In silico approach for predicting toxicity of peptides and proteins. PloS One 8, (2013).","DOI":"10.1371\/journal.pone.0073957"},{"key":"81736_CR28","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/978-1-4939-2285-7_7","volume":"1268","author":"S Gupta","year":"2015","unstructured":"Gupta, S. et al. Peptide toxicity prediction. Methods Mol. Biol. 1268, 143\u2013157 (2015).","journal-title":"Methods Mol. Biol."},{"key":"81736_CR29","doi-asserted-by":"publisher","first-page":"W443","DOI":"10.1093\/nar\/gky357","volume":"46","author":"P Zhou","year":"2018","unstructured":"Zhou, P., Jin, B., Li, H. & Huang, S. Y. HPEPDOCK: A web server for blind peptide\u2013protein docking based on a hierarchical algorithm. Nucleic Acids Res. 46, W443\u2013W450 (2018).","journal-title":"Nucleic Acids Res."},{"key":"81736_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-39299-8","volume":"9","author":"V Chauhan","year":"2019","unstructured":"Chauhan, V., Rungta, T., Goyal, K. & Singh, M. P. Designing a multi-epitope based vaccine to combat Kaposi Sarcoma utilizing immunoinformatics approach. Sci. Rep. 9, 1\u201315 (2019).","journal-title":"Sci. Rep."},{"key":"81736_CR31","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1016\/j.addr.2012.09.039","volume":"65","author":"X Chen","year":"2013","unstructured":"Chen, X., Zaro, J. L. & Shen, W. C. Fusion protein linkers: Property, design and functionality. Adv. Drug Deliv. Rev. 65, 1357\u20131369 (2013).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"81736_CR32","first-page":"43","volume":"15","author":"DAE Pitaloka","year":"2022","unstructured":"Pitaloka, D. A. E., Izzati, A., Amirah, S. R. & Syakuran, L. A. Multi epitope-based vaccine design for protection against mycobacterium tuberculosis and SARS-CoV-2 coinfection. Adv. Appl. Bioinforma. Chem. AABC 15, 43\u201357 (2022).","journal-title":"Adv. Appl. Bioinforma. Chem. AABC"},{"key":"81736_CR33","first-page":"1","volume":"40","author":"VS Ayyagari","year":"2020","unstructured":"Ayyagari, V. S., Venkateswarulu, T. C., Abraham Peele, K. & Srirama, K. Design of a multi-epitope-based vaccine targeting M-protein of SARS-CoV2: an immunoinformatics approach. J. Biomol. Struct. Dyn. 40, 1 (2020).","journal-title":"J. Biomol. Struct. Dyn."},{"key":"81736_CR34","doi-asserted-by":"publisher","first-page":"2322","DOI":"10.1016\/j.vaccine.2005.01.031","volume":"23","author":"A Yano","year":"2005","unstructured":"Yano, A. et al. An ingenious design for peptide vaccines. Vaccine 23, 2322\u20132326 (2005).","journal-title":"Vaccine"},{"key":"81736_CR35","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/978-1-61737-967-3_16","volume":"705","author":"P Sun","year":"2011","unstructured":"Sun, P., Tropea, J. E. & Waugh, D. S. Enhancing the solubility of recombinant proteins in Escherichia coli by using hexahistidine-tagged maltose-binding protein as a fusion partner. Methods Mol. Biol. Clifton NJ 705, 259\u2013274 (2011).","journal-title":"Methods Mol. Biol. Clifton NJ"},{"key":"81736_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-8-361","volume":"8","author":"HH Bui","year":"2007","unstructured":"Bui, H. H., Sidney, J., Li, W., Fusseder, N. & Sette, A. Development of an epitope conservancy analysis tool to facilitate the design of epitope-based diagnostics and vaccines. BMC Bioinformatics 8, 1\u20136 (2007).","journal-title":"BMC Bioinformatics"},{"key":"81736_CR37","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.ygeno.2017.05.001","volume":"109","author":"MI Rashid","year":"2017","unstructured":"Rashid, M. I., Naz, A., Ali, A. & Andleeb, S. Prediction of vaccine candidates against Pseudomonas aeruginosa: An integrated genomics and proteomics approach. Genomics 109, 274\u2013283 (2017).","journal-title":"Genomics"},{"key":"81736_CR38","doi-asserted-by":"publisher","DOI":"10.1385\/1-59259-890-0:571","author":"JM Walker","year":"2005","unstructured":"Walker, J. M. et al. Protein identification and analysis tools on the ExPASy server. Proteomics Protoc. Handb. https:\/\/doi.org\/10.1385\/1-59259-890-0:571 (2005).","journal-title":"Proteomics Protoc. Handb."},{"key":"81736_CR39","doi-asserted-by":"publisher","first-page":"3098","DOI":"10.1093\/bioinformatics\/btx345","volume":"33","author":"M Hebditch","year":"2017","unstructured":"Hebditch, M., Carballo-Amador, M. A., Charonis, S., Curtis, R. & Warwicker, J. Protein\u2013Sol: a web tool for predicting protein solubility from sequence. Bioinformatics 33, 3098\u20133100 (2017).","journal-title":"Bioinformatics"},{"key":"81736_CR40","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1093\/bioinformatics\/btq551","volume":"26","author":"CN Magnan","year":"2010","unstructured":"Magnan, C. N. et al. High-throughput prediction of protein antigenicity using protein microarray data. Bioinformatics 26, 2936 (2010).","journal-title":"Bioinformatics"},{"key":"81736_CR41","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-014-2278-5","author":"I Dimitrov","year":"2014","unstructured":"Dimitrov, I., Bangov, I., Flower, D. R. & Doytchinova, I. AllerTOP vol 2\u2013a server for in silico prediction of allergens. J. Mol. Model. https:\/\/doi.org\/10.1007\/s00894-014-2278-5 (2014).","journal-title":"J. Mol. Model."},{"key":"81736_CR42","doi-asserted-by":"publisher","first-page":"W402","DOI":"10.1093\/nar\/gkz297","volume":"47","author":"DWA Buchan","year":"2019","unstructured":"Buchan, D. W. A. & Jones, D. T. The PSIPRED protein analysis workbench: 20 years on. Nucleic Acids Res. 47, W402\u2013W407 (2019).","journal-title":"Nucleic Acids Res."},{"key":"81736_CR43","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1093\/bioinformatics\/11.6.681","volume":"11","author":"C Geourjon","year":"1995","unstructured":"Geourjon, C. & Del\u00e9age, G. SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments. Bioinformatics 11, 681\u2013684 (1995).","journal-title":"Bioinformatics"},{"issue":"1","key":"81736_CR44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-016-0001-8","volume":"6","author":"S Wang","year":"2016","unstructured":"Wang, S., Peng, J., Ma, J. & Xu, J. Protein secondary structure prediction using deep convolutional neural fields. Sci. Rep. 6(1), 1\u201311 (2016).","journal-title":"Sci. Rep."},{"key":"81736_CR45","doi-asserted-by":"publisher","first-page":"W174","DOI":"10.1093\/nar\/gkv342","volume":"43","author":"J Yang","year":"2015","unstructured":"Yang, J. & Zhang, Y. I-TASSER server: New development for protein structure and function predictions. Nucleic Acids Res. 43, W174\u2013W181 (2015).","journal-title":"Nucleic Acids Res."},{"key":"81736_CR46","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s10989-022-10406-0","volume":"28","author":"M Ghandadi","year":"2022","unstructured":"Ghandadi, M. An immunoinformatic strategy to develop new mycobacterium tuberculosis multi-epitope vaccine. Int. J. Pept. Res. Ther. 28, 99 (2022).","journal-title":"Int. J. Pept. Res. Ther."},{"key":"81736_CR47","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.1016\/j.bpj.2011.10.024","volume":"101","author":"D Xu","year":"2011","unstructured":"Xu, D. & Zhang, Y. Improving the physical realism and structural accuracy of protein models by a two-step atomic-level energy minimization. Biophys. J. 101, 2525 (2011).","journal-title":"Biophys. J."},{"key":"81736_CR48","first-page":"1","volume":"2","author":"W-H Shin","year":"2014","unstructured":"Shin, W.-H., Lee, G. R., Heo, L., Lee, H. & Seok, C. Prediction of protein structure and interaction by GALAXY protein modeling programs. BioDesign 2, 1\u201311 (2014).","journal-title":"BioDesign"},{"key":"81736_CR49","doi-asserted-by":"publisher","first-page":"W384","DOI":"10.1093\/nar\/gkt458","volume":"41","author":"L Heo","year":"2013","unstructured":"Heo, L., Park, H. & Seok, C. GalaxyRefine: Protein structure refinement driven by side-chain repacking. Nucleic Acids Res. 41, W384 (2013).","journal-title":"Nucleic Acids Res."},{"key":"81736_CR50","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1016\/j.ijbiomac.2020.07.117","volume":"164","author":"S Sanami","year":"2020","unstructured":"Sanami, S. et al. Design of a multi-epitope vaccine against SARS-CoV-2 using immunoinformatics approach. Int. J. Biol. Macromol. 164, 871\u2013883 (2020).","journal-title":"Int. J. Biol. Macromol."},{"key":"81736_CR51","doi-asserted-by":"publisher","first-page":"W407","DOI":"10.1093\/nar\/gkm290","volume":"35","author":"M Wiederstein","year":"2007","unstructured":"Wiederstein, M. & Sippl, M. J. ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res. 35, W407\u2013W410 (2007).","journal-title":"Nucleic Acids Res."},{"key":"81736_CR52","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1002\/pro.5560020916","volume":"2","author":"C Colovos","year":"1993","unstructured":"Colovos, C. & Yeates, T. O. Verification of protein structures: Patterns of nonbonded atomic interactions. Protein Sci. Publ. Protein Soc. 2, 1511\u20131519 (1993).","journal-title":"Protein Sci. Publ. Protein Soc."},{"key":"81736_CR53","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1126\/science.1853201","volume":"253","author":"JU Bowie","year":"1991","unstructured":"Bowie, J. U., L\u00fcthy, R. & Eisenberg, D. A method to identify protein sequences that fold into a known three-dimensional structure. Science 253, 164\u2013170 (1991).","journal-title":"Science"},{"key":"81736_CR54","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1107\/S0021889892009944","volume":"26","author":"RA Laskowski","year":"1993","unstructured":"Laskowski, R. A., MacArthur, M. W., Moss, D. S. & Thornton, J. M. PROCHECK: A program to check the stereochemical quality of protein structures. J. Appl. Crystallogr. 26, 283\u2013291 (1993).","journal-title":"J. Appl. Crystallogr."},{"key":"81736_CR55","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1515\/bmc.2010.022","volume":"1","author":"SA Hollingsworth","year":"2010","unstructured":"Hollingsworth, S. A. & Karplus, P. A. A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins. Biomol. Concepts 1, 271\u2013283 (2010).","journal-title":"Biomol. Concepts"},{"key":"81736_CR56","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.febslet.2013.11.024","volume":"588","author":"AA Dombkowski","year":"2014","unstructured":"Dombkowski, A. A., Sultana, K. Z. & Craig, D. B. Protein disulfide engineering. FEBS Lett. 588, 206\u2013212 (2014).","journal-title":"FEBS Lett."},{"key":"81736_CR57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-14-S19-S1","volume":"14","author":"DB Craig","year":"2013","unstructured":"Craig, D. B. & Dombkowski, A. A. Disulfide by Design 2.0: A web-based tool for disulfide engineering in proteins. BMC Bioinformatics 14, 1\u20137 (2013).","journal-title":"BMC Bioinformatics"},{"key":"81736_CR58","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2105-9-514","volume":"9","author":"J Ponomarenko","year":"2008","unstructured":"Ponomarenko, J. et al. ElliPro: A new structure-based tool for the prediction of antibody epitopes. BMC Bioinformatics 9, 1\u20138 (2008).","journal-title":"BMC Bioinformatics"},{"key":"81736_CR59","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1745-6150-8-30","volume":"8","author":"SK Dhanda","year":"2013","unstructured":"Dhanda, S. K., Vir, P. & Raghava, G. P. S. Designing of interferon-gamma inducing MHC class-II binders. Biol. Direct. 8, 30 (2013).","journal-title":"Biol. Direct."},{"issue":"7","key":"81736_CR60","first-page":"1","volume":"2017","author":"G Nagpal","year":"2017","unstructured":"Nagpal, G. et al. Computer-aided designing of immunosuppressive peptides based on IL-10 inducing potential. Sci. Rep. 2017(7), 1\u201310 (2017).","journal-title":"Sci. Rep."},{"key":"81736_CR61","doi-asserted-by":"publisher","first-page":"3352","DOI":"10.1093\/nar\/gkg512","volume":"31","author":"TA Binkowski","year":"2003","unstructured":"Binkowski, T. A., Naghibzadeh, S. & Liang, J. CASTp: Computed Atlas of Surface Topography of proteins. Nucleic Acids Res. 31, 3352 (2003).","journal-title":"Nucleic Acids Res."},{"key":"81736_CR62","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/0010-4655(95)00042-E","volume":"91","author":"HJC Berendsen","year":"1995","unstructured":"Berendsen, H. J. C., van der Spoel, D. & van Drunen, R. GROMACS: A message-passing parallel molecular dynamics implementation. Comput. Phys. Commun. 91, 43\u201356 (1995).","journal-title":"Comput. Phys. Commun."},{"key":"81736_CR63","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1021\/ci500020m","volume":"54","author":"R Kumari","year":"2014","unstructured":"Kumari, R., Kumar, R. & Lynn, A. G-mmpbsa -A GROMACS tool for high-throughput MM-PBSA calculations. J. Chem. Inf. Model. 54, 1951\u20131962 (2014).","journal-title":"J. Chem. Inf. Model."},{"key":"81736_CR64","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.tips.2022.09.008","volume":"44","author":"BC Lin","year":"2023","unstructured":"Lin, B. C., Kaissarian, N. M. & Kimchi-Sarfaty, C. Implementing computational methods in tandem with synonymous gene recoding for therapeutic development. Trends Pharmacol. Sci. 44, 73\u201384 (2023).","journal-title":"Trends Pharmacol. Sci."},{"key":"81736_CR65","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1093\/bioinformatics\/btr335","volume":"27","author":"N Rapin","year":"2011","unstructured":"Rapin, N., Lund, O. & Castiglione, F. Immune system simulation online. Bioinformatics 27, 2013\u20132014 (2011).","journal-title":"Bioinformatics"},{"key":"81736_CR66","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.it.2016.08.010","volume":"37","author":"KL Rock","year":"2016","unstructured":"Rock, K. L., Reits, E. & Neefjes, J. Present Yourself! By MHC Class I and MHC Class II Molecules. Trends Immunol. 37, 724 (2016).","journal-title":"Trends Immunol."},{"issue":"11","key":"81736_CR67","first-page":"1","volume":"2021","author":"A Albutti","year":"2021","unstructured":"Albutti, A. An integrated computational framework to design a multi-epitopes vaccine against Mycobacterium tuberculosis. Sci. Rep. 2021(11), 1\u201318 (2021).","journal-title":"Sci. Rep."},{"key":"81736_CR68","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3390\/proteomes5010004","volume":"5","author":"MR Pergande","year":"2017","unstructured":"Pergande, M. R., Cologna, S. M., Coorssen, J. R., Yergey, A. L. & Wisniewski, J. R. Isoelectric point separations of peptides and proteins. Proteomes 5, 4 (2017).","journal-title":"Proteomes"},{"key":"81736_CR69","unstructured":"Thermostability and Aliphatic Index of Globular Proteins. https:\/\/www.jstage.jst.go.jp\/article\/biochemistry1922\/88\/6\/88_6_1895\/_article."},{"key":"81736_CR70","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.ijbiomac.2019.07.024","volume":"138","author":"P Kalita","year":"2019","unstructured":"Kalita, P., Lyngdoh, D. L., Padhi, A. K., Shukla, H. & Tripathi, T. Development of multi-epitope driven subunit vaccine against Fasciola gigantica using immunoinformatics approach. Int. J. Biol. Macromol. 138, 224\u2013233 (2019).","journal-title":"Int. J. Biol. Macromol."},{"key":"81736_CR71","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1002\/prot.20264","volume":"57","author":"Y Zhang","year":"2004","unstructured":"Zhang, Y. & Skolnick, J. Scoring function for automated assessment of protein structure template quality. Proteins 57, 702\u2013710 (2004).","journal-title":"Proteins"},{"key":"81736_CR72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13205-022-03286-0","volume":"12","author":"A Kumar","year":"2022","unstructured":"Kumar, A., Rathi, E. & Kini, S. G. Computational design of a broad-spectrum multi-epitope vaccine candidate against seven strains of human coronaviruses. 3 Biotech 12, 1\u201317 (2022).","journal-title":"3 Biotech"},{"key":"81736_CR73","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1007\/s12026-023-09374-4","volume":"71","author":"J Dey","year":"2023","unstructured":"Dey, J. et al. Designing of multi-epitope peptide vaccine against Acinetobacter baumannii through combined immunoinformatics and protein interaction\u2013based approaches. Immunol. Res. 71, 639\u2013662 (2023).","journal-title":"Immunol. Res."},{"key":"81736_CR74","unstructured":"Charles A Janeway, J., Travers, P., Walport, M. & Shlomchik, M. J. Immunobiology. Immunobiology 1\u201310 (2001)."},{"key":"81736_CR75","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/44385","volume":"401","author":"F Sallusto","year":"1999","unstructured":"Sallusto, F., Lenig, D., F\u00f6rster, R., Lipp, M. & Lanzavecchia, A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708\u2013712 (1999).","journal-title":"Nature"},{"key":"81736_CR76","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1086\/589862","volume":"47","author":"SA Plotkin","year":"2008","unstructured":"Plotkin, S. A. Vaccines: correlates of vaccine-induced immunity. Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am. 47, 401\u2013409 (2008).","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"81736_CR77","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1038\/383787a0","volume":"383","author":"AK Abbas","year":"1996","unstructured":"Abbas, A. K., Murphy, K. M. & Sher, A. Functional diversity of helper T lymphocytes. Nature 383, 787\u2013793 (1996).","journal-title":"Nature"},{"key":"81736_CR78","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.clim.2009.01.009","volume":"131","author":"AS De Groot","year":"2009","unstructured":"De Groot, A. S. & Martin, W. Reducing risk, improving outcomes: bioengineering less immunogenic protein therapeutics. Clin. Immunol. Orlando Fla 131, 189\u2013201 (2009).","journal-title":"Clin. Immunol. Orlando Fla"},{"key":"81736_CR79","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1016\/S1369-5274(00)00119-3","volume":"3","author":"R Rappuoli","year":"2000","unstructured":"Rappuoli, R. Reverse vaccinology. Curr. Opin. Microbiol. 3, 445\u2013450 (2000).","journal-title":"Curr. Opin. Microbiol."},{"key":"81736_CR80","doi-asserted-by":"publisher","DOI":"10.1007\/S12033-023-00949-Y\/FIGURES\/11","author":"A Ullah","year":"2023","unstructured":"Ullah, A. et al. An in silico multi-epitopes vaccine ensemble and characterization against nosocomial Proteus penneri. Mol. Biotechnol. https:\/\/doi.org\/10.1007\/S12033-023-00949-Y\/FIGURES\/11 (2023).","journal-title":"Mol. Biotechnol."},{"key":"81736_CR81","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2258403","author":"S Ahmad","year":"2023","unstructured":"Ahmad, S. et al. Computational design of a multi-epitope vaccine candidate against Langya henipavirus using surface proteins. J. Biomol. Struct. Dyn. https:\/\/doi.org\/10.1080\/07391102.2023.2258403 (2023).","journal-title":"J. Biomol. Struct. Dyn."},{"key":"81736_CR82","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s40203-023-00156-2","volume":"11","author":"AR Yaseen","year":"2023","unstructured":"Yaseen, A. R. et al. Development of conserved multi-epitopes based hybrid vaccine against SARS-CoV-2 variants: an immunoinformatic approach. Silico Pharmacol. 11, 18 (2023).","journal-title":"Silico Pharmacol."},{"key":"81736_CR83","doi-asserted-by":"publisher","first-page":"e0244176","DOI":"10.1371\/journal.pone.0244176","volume":"15","author":"M Tahir Ul Qamar","year":"2020","unstructured":"Tahir Ul Qamar, M. et al. Designing of a next generation multiepitope based vaccine (MEV) against SARS-COV-2: Immunoinformatics and in silico approaches. PloS One 15, e0244176 (2020).","journal-title":"PloS One"},{"key":"81736_CR84","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01096-23","volume":"97","author":"L Zayou","year":"2023","unstructured":"Zayou, L. et al. A multi-epitope\/CXCL11 prime\/pull coronavirus mucosal vaccine boosts the frequency and the function of lung-resident memory CD4+ and CD8+ T cells and enhanced protection against COVID-19-like symptoms and death caused by SARS-CoV-2 infection. J. Virol. 97, e0109623 (2023).","journal-title":"J. Virol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-81736-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-81736-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-81736-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T13:05:33Z","timestamp":1733144733000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-81736-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,2]]},"references-count":84,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["81736"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-81736-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,2]]},"assertion":[{"value":"26 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29919"}}