{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:40:08Z","timestamp":1792629608710,"version":"4.5.0"},"reference-count":101,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Latent tuberculosis infection (LTBI) is the principal reservoir for active tuberculosis, with &gt;85% of cases attributable to reactivation. Bacillus Calmette-Gu\u00e9rin fails to block this transition, leaving a critical gap in prevention. Methods: An immunoinformatics\/reverse-vaccinology pipeline was applied to seven dormancy-related antigens retrieved from Mycobrowser. T-cell epitopes were predicted with NetMHCI\/IIpan-4.1 and B-cell epitopes with ABCpred; antigenicity, allergenicity, and toxicity were evaluated with VaxiJen, AllerTOP, and ToxinPred. Secondary\/tertiary structures were modeled with PSIPRED and AlphaFold-3; docking to Toll-like receptors (TLR) 2\/4 and 100 ns molecular dynamics simulations assessed complex stability. Immune responses were simulated with C-ImmSim, and the mRNA sequence was human-codon-optimized using ExpOptimizer. Results: The resulting construct, RP14914P, encodes 14 cytotoxic T lymphocyte, 9 helper T lymphocyte, and 14 B-cell epitopes within an 866-aa, 90.4 kDa polypeptide. Antigenicity score = 0.7797, immunogenicity score = 8.58629. and no toxicity or allergenicity was predicted. Physicochemical analysis: instability index = 28.65, and solubility = 0.513. Estimated population coverage is 82.35% and 99.67% for Human Leukocyte Antigen (HLA)-I and HLA-II globally. Docking energies: \u22121477.8 kcal\/mol (TLR2) and \u22121480.1 kcal\/mol (TLR4). Molecular dynamics trajectories confirm stable binding. Immune simulation predicts potent activation of Natural Killer cells, macrophages, and dendritic cells, Th1 polarization, high interferon-\u03b3\/interleukin-2 secretion, and durable memory. Conclusions: In silico analyses predict that RP14914P exhibits favorable immunogenicity, safety, and broad population coverage, suggesting its potential as a promising mRNA vaccine candidate to prevent LTBI reactivation. However, these computational predictions require thorough experimental validation to confirm the vaccine\u2019s immunogenicity and protective efficacy.<\/jats:p>","DOI":"10.3390\/pathogens15030297","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:16:12Z","timestamp":1773051372000},"page":"297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunoinformatic Design and Evaluation of a Multi-Epitope mRNA Vaccine RP14914P Targeting Latent Tuberculosis Infection"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7407-3126","authenticated-orcid":false,"given":"Yuan","family":"Tian","sequence":"first","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"},{"name":"Graduate School, Hebei North University, Zhangjiakou 075000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7229-5242","authenticated-orcid":false,"given":"Mingming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"},{"name":"Graduate School, Hebei North University, Zhangjiakou 075000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0298-1848","authenticated-orcid":false,"given":"Syed Luqman","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Abdul Wali Khan University, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aigul","family":"Abduldayeva","sequence":"additional","affiliation":[{"name":"Department of Research Institute of Preventive Medicine Named Academician E. Dalenov, Astana Medical University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4940-5061","authenticated-orcid":false,"given":"Shuang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"},{"name":"Graduate School, Hebei North University, Zhangjiakou 075000, China"},{"name":"Department of Geriatrics, The Eighth Medical Center of PLA General Hospital, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7016-0008","authenticated-orcid":false,"given":"Yajing","family":"An","sequence":"additional","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"},{"name":"Graduate School, Hebei North University, Zhangjiakou 075000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2483-1267","authenticated-orcid":false,"given":"Yufeng","family":"Li","sequence":"additional","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"},{"name":"Graduate School, Hebei North University, Zhangjiakou 075000, China"},{"name":"Department of Geriatrics, The Eighth Medical Center of PLA General Hospital, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2522-0257","authenticated-orcid":false,"given":"Ruizi","family":"Ni","sequence":"additional","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"},{"name":"Graduate School, Hebei North University, Zhangjiakou 075000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6596-2847","authenticated-orcid":false,"given":"Lingxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8095-3930","authenticated-orcid":false,"given":"Yanhua","family":"Liu","sequence":"additional","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Sun","sequence":"additional","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0333-890X","authenticated-orcid":false,"given":"Wenping","family":"Gong","sequence":"additional","affiliation":[{"name":"Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China"},{"name":"Graduate School, Hebei North University, Zhangjiakou 075000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70054","DOI":"10.1002\/imt2.70054","article-title":"Gut microbiota and tuberculosis","volume":"4","author":"Liu","year":"2025","journal-title":"IMeta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15212\/ZOONOSES-2024-0061","article-title":"Decoding the WHO Global Tuberculosis Report 2024: A Critical Analysis of Global and Chinese Key Data","volume":"5","author":"Chen","year":"2025","journal-title":"Zoonoses"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s43556-024-00243-6","article-title":"Tuberculosis vaccines and therapeutic drug: Challenges and future directions","volume":"6","author":"An","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s40124-014-0054-8","article-title":"Current Diagnosis and Treatment of Pediatric Latent Tuberculosis Infection","volume":"2","author":"Hatzenbuehler","year":"2014","journal-title":"Curr. Pediatr. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.4081\/monaldi.2024.3156","article-title":"Novel tuberculosis skin tests for detecting latent tuberculosis infection","volume":"95","author":"Doshi","year":"2024","journal-title":"Monaldi Arch. Chest Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1111\/resp.13346","article-title":"Latent tuberculosis infection: Opportunities and challenges","volume":"23","author":"Chee","year":"2018","journal-title":"Respirology"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Carranza, C., Pedraza-Sanchez, S., de Oyarzabal-Mendez, E., and Torres, M. (2020). Diagnosis for Latent Tuberculosis Infection: New Alternatives. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.02006"},{"key":"ref_8","unstructured":"WHO (2025). Global Tuberculosis Report 2025, World Health Organization."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Gong, W., and Wu, X. (2021). Differential Diagnosis of Latent Tuberculosis Infection and Active Tuberculosis: A Key to a Successful Tuberculosis Control Strategy. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.745592"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/cid\/cit790","article-title":"Protection by BCG vaccine against tuberculosis: A systematic review of randomized controlled trials","volume":"58","author":"Mangtani","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhuang, L., Ye, Z., Li, L., Yang, L., and Gong, W. (2023). Next-Generation TB Vaccines: Progress, Challenges, and Prospects. Vaccines, 11.","DOI":"10.3390\/vaccines11081304"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1056\/NEJMoa1909953","article-title":"Final Analysis of a Trial of M72\/AS01(E) Vaccine to Prevent Tuberculosis","volume":"381","author":"Tait","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4130","DOI":"10.1016\/j.vaccine.2015.06.051","article-title":"First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults","volume":"33","author":"Luabeya","year":"2015","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nm.2285","article-title":"A multistage tuberculosis vaccine that confers efficient protection before and after exposure","volume":"17","author":"Aagaard","year":"2011","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev-immunol-032712-095939","article-title":"The immune response in tuberculosis","volume":"31","author":"Redford","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e70212","DOI":"10.1111\/1751-7915.70212","article-title":"Harnessing the Potential of mRNA Vaccines Against Infectious Diseases","volume":"18","author":"Rezk","year":"2025","journal-title":"Microb. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sethi, G., Kim, Y.K., Han, S.C., and Hwang, J.H. (2024). Designing a broad-spectrum multi-epitope subunit vaccine against leptospirosis using immunoinformatics and structural approaches. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1503853"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1080\/07391102.2020.1846625","article-title":"Designing a novel multiepitope peptide vaccine against melanoma using immunoinformatics approach","volume":"40","author":"Yazdani","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.synbio.2024.05.008","article-title":"Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches","volume":"9","author":"Tan","year":"2024","journal-title":"Synth. Syst. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s10930-023-10150-4","article-title":"Computer-Aided Multi-Epitope Based Vaccine Design Against Monkeypox Virus Surface Protein A30L: An Immunoinformatics Approach","volume":"42","author":"Ramprasadh","year":"2023","journal-title":"Protein J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10761","DOI":"10.1080\/07391102.2023.2258420","article-title":"Designing a novel multi-epitopes pan-vaccine against SARS-CoV-2 and seasonal influenza: In silico and immunoinformatics approach","volume":"42","author":"Fathollahi","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhang, M., Ali, S.L., Tian, Y., Abduldayeva, A., Zhou, S., An, Y., Li, Y., Ni, R., Zhang, L., and Liu, Y. (2025). EP9158H: An Immunoinformatics-Designed mRNA Vaccine Encoding Multi-Epitope Antigens and Dual TLR Agonists for Tuberculosis Prevention. Bioengineering, 12.","DOI":"10.3390\/bioengineering12121378"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1007\/s11030-022-10515-4","article-title":"Modeling of MT. P495, an mRNA-based vaccine against the phosphate-binding protein PstS1 of Mycobacterium tuberculosis","volume":"27","author":"Shahrear","year":"2022","journal-title":"Mol. Divers."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Xu, S., Yang, K., Li, R., and Zhang, L. (2020). mRNA Vaccine Era-Mechanisms, Drug Platform and Clinical Prospection. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186582"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1128\/IAI.01235-07","article-title":"Mycobacterium bovis BCG vaccine strains lack narK2 and narX induction and exhibit altered phenotypes during dormancy","volume":"76","author":"Honaker","year":"2008","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cao, X.J., Li, Y.P., Wang, J.Y., Zhou, J., and Guo, X.G. (2021). MPT64 assays for the rapid detection of Mycobacterium tuberculosis. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06022-w"},{"key":"ref_27","unstructured":"Bai, X. (2014). Preparation of Four Tuberculosis Latent Proteins and the Evaluation of Their Immunological Characteristic. [Doctoral Dissertation, Medical School of Chinese PLA]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.1128\/IAI.01436-08","article-title":"Frequencies of region of difference 1 antigen-specific but not purified protein derivative-specific gamma interferon-secreting T cells correlate with the presence of tuberculosis disease but do not distinguish recent from remote latent infections","volume":"77","author":"Hinks","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1469-0691.2006.01660.x","article-title":"The RD1-encoded antigen Rv3872 of Mycobacterium tuberculosis as a potential candidate for serodiagnosis of tuberculosis","volume":"13","author":"Mukherjee","year":"2007","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1684\/ecn.2017.0391","article-title":"Interferon Gamma Release Assay in response to PE35\/PPE68 proteins: A promising diagnostic method for diagnosis of latent tuberculosis","volume":"28","author":"Mahmoudi","year":"2017","journal-title":"Eur. Cytokine Netw."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"W449","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: Improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kaabinejadian, S., Barra, C., Alvarez, B., Yari, H., Hildebrand, W.H., and Nielsen, M. (2022). Accurate MHC Motif Deconvolution of Immunopeptidomics Data Reveals a Significant Contribution of DRB3, 4 and 5 to the Total DR Immunopeptidome. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.835454"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111144","DOI":"10.1016\/j.compbiomed.2025.111144","article-title":"Immunoinformatics-driven construction of a next-generation epitope-based vaccine from conserved hypothetical proteins of M. tuberculosis for enhanced TB control","volume":"198","author":"Arif","year":"2025","journal-title":"Comput. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"263952","DOI":"10.1155\/2013\/263952","article-title":"Prediction of IL4 inducing peptides","volume":"2013","author":"Dhanda","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"42851","DOI":"10.1038\/srep42851","article-title":"Computer-aided designing of immunosuppressive peptides based on IL-10 inducing potential","volume":"7","author":"Nagpal","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/prot.21078","article-title":"Prediction of continuous B-cell epitopes in an antigen using recurrent neural network","volume":"65","author":"Saha","year":"2006","journal-title":"Proteins"},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1007\/s00894-014-2278-5","article-title":"AllerTOP v.2\u2014A server for in silico prediction of allergens","volume":"20","author":"Dimitrov","year":"2014","journal-title":"J. Mol. Model."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"bbac174","DOI":"10.1093\/bib\/bbac174","article-title":"ToxinPred2: An improved method for predicting toxicity of proteins","volume":"23","author":"Sharma","year":"2022","journal-title":"Brief. Bioinform."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Shi, H., Zhu, Y., Shang, K., Tian, T., Yin, Z., Shi, J., He, Y., Ding, J., Wang, Q., and Zhang, F. (2024). Development of innovative multi-epitope mRNA vaccine against central nervous system tuberculosis using in silico approaches. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0307877"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Reshetnikov, V., Terenin, I., Shepelkova, G., Yeremeev, V., Kolmykov, S., Nagornykh, M., Kolosova, E., Sokolova, T., Zaborova, O., and Kukushkin, I. (2024). Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020888"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109130","DOI":"10.1016\/j.jmgm.2025.109130","article-title":"Structure-based design of a multi-epitope vaccine candidate against marburg virus using immunoinformatics and dynamics simulations","volume":"141","author":"Saadh","year":"2025","journal-title":"J. Mol. Graph. Model."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1093\/bioinformatics\/btx345","article-title":"Protein-Sol: A web tool for predicting protein solubility from sequence","volume":"33","author":"Hebditch","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1007\/s10989-019-09916-1","article-title":"Prediction of potential epitopes for peptide vaccine formulation against teschovirus a using immunoinformatics","volume":"26","author":"Barman","year":"2020","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"38391","DOI":"10.1039\/C9RA05218F","article-title":"Protein secondary structure prediction with context convolutional neural network","volume":"9","author":"Long","year":"2019","journal-title":"RSC Adv."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/bioinformatics\/16.4.404","article-title":"The PSIPRED protein structure prediction server","volume":"16","author":"McGuffin","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"394","DOI":"10.47665\/tb.39.3.009","article-title":"In silico structural modeling and quality assessment of Plasmodium knowlesi apical membrane antigen 1 using comparative protein models","volume":"39","author":"Haron","year":"2022","journal-title":"Trop. Biomed."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Muccee, F., Ghazanfar, S., Ajmal, W., and Al-Zahrani, M. (2022). In-silico characterization of estrogen reactivating \u03b2-glucuronidase enzyme in git associated microbiota of normal human and breast cancer patients. Genes, 13.","DOI":"10.3390\/genes13091545"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Gong, W., Liang, Y., Mi, J., Jia, Z., Xue, Y., Wang, J., Wang, L., Zhou, Y., Sun, S., and Wu, X. (2021). Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.666290"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.ijtb.2021.08.016","article-title":"A peptide-based vaccine ACP derived from antigens of Mycobacterium tuberculosis induced Th1 response but failed to enhance the protective efficacy of BCG in mice","volume":"69","author":"Gong","year":"2022","journal-title":"Indian J. Tuberc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1007\/s12033-022-00560-7","article-title":"Comprehensive Molecular Interaction Studies to Construe the Repellent\/Kill Activity of Geraniol During Binding Event Against Aedes aegypti Proteins","volume":"65","author":"Setlur","year":"2023","journal-title":"Mol. Biotechnol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bui, H.H., Sidney, J., Dinh, K., Southwood, S., Newman, M.J., and Sette, A. (2006). Predicting population coverage of T-cell epitope-based diagnostics and vaccines. BMC Bioinform., 7.","DOI":"10.1186\/1471-2105-7-153"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ponomarenko, J., Bui, H.H., Li, W., Fusseder, N., Bourne, P.E., Sette, A., and Peters, B. (2008). ElliPro: A new structure-based tool for the prediction of antibody epitopes. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-514"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1107\/S2059798322002741","article-title":"Elucidation of protein function using computational docking and hotspot analysis by ClusPro and FTMap","volume":"78","author":"Jones","year":"2022","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1007\/s12033-023-00949-y","article-title":"An In Silico Multi-epitopes Vaccine Ensemble and Characterization Against Nosocomial Proteus penneri","volume":"66","author":"Ullah","year":"2024","journal-title":"Mol. Biotechnol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1186\/s40001-025-03013-4","article-title":"Deferoxamine addresses metabolic dysregulation and urinary tract infections in weight-associated gestational diabetes mellitus","volume":"30","author":"Zhang","year":"2025","journal-title":"Eur. J. Med. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5297","DOI":"10.1007\/s12013-025-01849-5","article-title":"Bioisosteric and Virtual Screening Approach to Identify Natural Inhibitors of Chikunguya alphavirus nsP3","volume":"83","author":"Lopes","year":"2025","journal-title":"Cell Biochem. Biophys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"111174","DOI":"10.1016\/j.compbiomed.2025.111174","article-title":"Disruption of histidine biosynthesis in Acinetobacter baumannii by Tubuloside B from Cistanche tubulosa","volume":"198","author":"Singh","year":"2025","journal-title":"Comput. Biol. Med."},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jiph.2022.11.033","article-title":"Designing multi-epitope monkeypox virus-specific vaccine using immunoinformatics approach","volume":"16","author":"Zaib","year":"2023","journal-title":"J. Infect. Public Health"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/nar\/9.1.133","article-title":"Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information","volume":"9","author":"Zuker","year":"1981","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12584","DOI":"10.1038\/s41598-022-16445-3","article-title":"An in silico approach to study the role of epitope order in the multi-epitope-based peptide (MEBP) vaccine design","volume":"12","author":"Salaikumaran","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.virusres.2009.09.007","article-title":"HIV-1 derived peptides fused to HBsAg affect its immunogenicity","volume":"146","author":"Gonzalez","year":"2009","journal-title":"Virus Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e70074","DOI":"10.1002\/iid3.70074","article-title":"Bioinformatics Analysis and Immunogenicity Assessment of the Novel Multi-Stage DNA Vaccine W541 Against Mycobacterium Tuberculosis","volume":"12","author":"Yang","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1021\/acs.jproteome.4c00989","article-title":"Multiomics and Machine Learning Identify Immunometabolic Biomarkers for Active Tuberculosis Diagnosis Against Nontuberculous Mycobacteria and Latent Tuberculosis Infection","volume":"24","author":"Tien","year":"2025","journal-title":"J. Proteome Res."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Pitua, I., Ssekamatte, P., Sitenda, D., Andia-Biraro, I., and Jonani, B. (2025). Agreement and systematic bias between QuantiFERON\u2013chemiluminescent immunoassay and QuantiFERON\u2013enzyme-linked immunosorbent assay in the detection of latent tuberculosis infection: A systematic review and meta-analysis. IJID Reg., 100824.","DOI":"10.1016\/j.ijregi.2025.100824"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.2147\/JIR.S451338","article-title":"Construction of Immune-Related Diagnostic Model for Latent Tuberculosis Infection and Active Tuberculosis","volume":"17","author":"Zhang","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Li, F., Dang, W., Du, Y., Xu, X., He, P., Zhou, Y., and Zhu, B. (2024). Tuberculosis Vaccines and T Cell Immune Memory. Vaccines, 12.","DOI":"10.3390\/vaccines12050483"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e867","DOI":"10.1002\/iid3.867","article-title":"Liposomal delivery system\/adjuvant for tuberculosis vaccine","volume":"11","author":"Moradi","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e28","DOI":"10.1016\/S1473-3099(19)30625-5","article-title":"The status of tuberculosis vaccine development","volume":"20","author":"Schrager","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Kazakova, A., Zhelnov, P., Sidorov, R., Rogova, A., Vasileva, O., Ivanov, R., Reshetnikov, V., and Muslimov, A. (2024). DNA and RNA vaccines against tuberculosis: A scoping review of human and animal studies. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1457327"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Kozlova, A., Pateev, I., Shepelkova, G., Vasileva, O., Zakharova, N., Yeremeev, V., Ivanov, R., and Reshetnikov, V. (2024). A Cap-Optimized mRNA Encoding Multiepitope Antigen ESAT6 Induces Robust Cellular and Humoral Immune Responses Against Mycobacterium tuberculosis. Vaccines, 12.","DOI":"10.3390\/vaccines12111267"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6324","DOI":"10.1128\/IAI.72.11.6324-6329.2004","article-title":"RNA encoding the MPT83 antigen induces protective immune responses against Mycobacterium tuberculosis infection","volume":"72","author":"Xue","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Lorenzi, J.C., Trombone, A.P., Rocha, C.D., Almeida, L.P., Lousada, R.L., Malardo, T., Fontoura, I.C., Rossetti, R.A., Gembre, A.F., and Silva, A.M. (2010). Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis. BMC Biotechnol., 10.","DOI":"10.1186\/1472-6750-10-77"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41541-024-00834-y","article-title":"Antigen identification strategies and preclinical evaluation models for advancing tuberculosis vaccine development","volume":"9","author":"Chugh","year":"2024","journal-title":"npj Vaccines"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Agrawal, N., Ates, L.S., Schille, S., Chaturvedi, A., Vogt, J., Vukovic, N., Vogel, A.B., Diekmann, J., Diken, M., and \u015eahin, U. (2025). mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well-tolerated and efficacious in rodent models. bioRxiv.","DOI":"10.1101\/2025.09.30.679428"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Jiang, F., Peng, C., Cheng, P., Wang, J., Lian, J., and Gong, W. (2023). PP19128R, a Multiepitope Vaccine Designed to Prevent Latent Tuberculosis Infection, Induced Immune Responses In Silico and In Vitro Assays. Vaccines, 11.","DOI":"10.3390\/vaccines11040856"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4645","DOI":"10.1038\/s41598-022-08506-4","article-title":"Novel In Silico mRNA vaccine design exploiting proteins of M. tuberculosis that modulates host immune responses by inducing epigenetic modifications","volume":"12","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"100148","DOI":"10.1016\/j.imj.2024.100148","article-title":"Leveraging computer-aided design and artificial intelligence to develop a next-generation multi-epitope tuberculosis vaccine candidate","volume":"3","author":"Zhuang","year":"2024","journal-title":"Infect. Med."},{"key":"ref_80","first-page":"754","article-title":"Multiepitope mRNA Vaccine mRNA-mEp21-FL-IDT Provides Efficient Protection against M. tuberculosis","volume":"90","author":"Kazakova","year":"2025","journal-title":"Biochemistry"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Nell, A.S., D\u2019Lom, E., Bouic, P., Sabat\u00e9, M., Bosser, R., Picas, J., Amat, M., Churchyard, G., and Cardona, P.J. (2014). Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: Randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089612"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nature12966","article-title":"Proof of principle for epitope-focused vaccine design","volume":"507","author":"Correia","year":"2014","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1186\/s12967-019-2116-8","article-title":"Epitope-based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: An immune-informatics study","volume":"17","author":"Saleem","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Sela-Culang, I., Kunik, V., and Ofran, Y. (2013). The structural basis of antibody-antigen recognition. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00302"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Cheng, P., Jiang, F., Wang, G., Wang, J., Xue, Y., Wang, L., and Gong, W. (2023). Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1102578"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.molcel.2014.03.012","article-title":"A cross-disciplinary perspective on the innate immune responses to bacterial lipopolysaccharide","volume":"54","author":"Tan","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"100796","DOI":"10.1016\/j.drup.2021.100796","article-title":"Anticancer drug resistance: An update and perspective","volume":"59","author":"Nussinov","year":"2021","journal-title":"Drug Resist. Updat."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.immuni.2010.02.008","article-title":"Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages","volume":"32","author":"Ghisletti","year":"2010","journal-title":"Immunity"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1146\/annurev-immunol-032712-095910","article-title":"Pathways of antigen processing","volume":"31","author":"Blum","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-immunol-030409-101212","article-title":"Differentiation of effector CD4 T cell populations (*)","volume":"28","author":"Zhu","year":"2010","journal-title":"Annu. Rev. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0065-2776(07)96002-2","article-title":"Regulation of interferon-gamma during innate and adaptive immune responses","volume":"96","author":"Schoenborn","year":"2007","journal-title":"Adv. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.immuni.2016.01.010","article-title":"In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity","volume":"44","author":"Halle","year":"2016","journal-title":"Immunity"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nri3307","article-title":"Transcriptional control of effector and memory CD8+ T cell differentiation","volume":"12","author":"Kaech","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.0105-2896.2006.00384.x","article-title":"Programming, demarcating, and manipulating CD8+ T-cell memory","volume":"211","author":"Badovinac","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1126\/science.1201730","article-title":"Different B cell populations mediate early and late memory during an endogenous immune response","volume":"331","author":"Pape","year":"2011","journal-title":"Science"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1128\/CVI.00131-10","article-title":"Correlates of protection induced by vaccination","volume":"17","author":"Plotkin","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Larsen, S.E., Erasmus, J.H., Reese, V.A., Pecor, T., Archer, J., Kandahar, A., Hsu, F.C., Nicholes, K., Reed, S.G., and Baldwin, S.L. (2023). An RNA-Based Vaccine Platform for Use against Mycobacterium tuberculosis. Vaccines, 11.","DOI":"10.3390\/vaccines11010130"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"102302","DOI":"10.1016\/j.tube.2022.102302","article-title":"Immunogenicity and protection against Mycobacterium avium with a heterologous RNA prime and protein boost vaccine regimen","volume":"138","author":"Rais","year":"2023","journal-title":"Tuberculosis"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Jiang, F., Han, Y., Liu, Y., Xue, Y., Cheng, P., Xiao, L., and Gong, W. (2023). A comprehensive approach to developing a multi-epitope vaccine against Mycobacterium tuberculosis: From in silico design to in vitro immunization evaluation. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1280299"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2300463","DOI":"10.1080\/22221751.2023.2300463","article-title":"A multistage Sendai virus vaccine incorporating latency-associated antigens induces protection against acute and latent tuberculosis","volume":"13","author":"Hu","year":"2024","journal-title":"Emerg. Microbes Infect."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Weng, S., Zhang, J., Ma, H., Zhou, J., Jia, L., Wan, Y., Cui, P., Ruan, Q., Shao, L., and Wu, J. (2022). B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1025931"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/3\/297\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:39:52Z","timestamp":1773052792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/3\/297"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":101,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["pathogens15030297"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15030297","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}