{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T18:19:07Z","timestamp":1765995547062,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-NHLBI","award":["2R15HL143545-02"],"award-info":[{"award-number":["2R15HL143545-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Tuberculosis (TB) remains a leading cause of mortality, with drug resistance highlighting the need for new vaccine targets. Peptidyl-prolyl isomerase A (PpiA), a conserved Mycobacterium tuberculosis (Mtb) protein, plays a role in bacterial stress adaptation and immune evasion, making it a potential target for immunotherapy. This study uses computational methods to assess PpiA\u2019s antigenicity, structural integrity, and immunogenic potential. The PpiA sequence was retrieved from NCBI and analyzed for antigenicity and allergenicity using VaxiJen, AllerTOP, and AllergenFP. Physicochemical properties were evaluated using ProtParam, and structural models were generated through PSIPRED and SWISS-MODEL. Structural validation was performed with MolProbity, QMEANDisCo, and ProSA-Web. B-cell epitopes were predicted using BepiPred 2.0 and IEDB, while T-cell epitopes were mapped via IEDB\u2019s MHC-I and MHC-II tools. Epitope conservation across Mtb strains was confirmed using ConSurf. Results indicate PpiA is highly antigenic, non-allergenic, and stable, with several immunogenic epitopes identified for both B- and T-cells. This study supports PpiA as a promising immunogenic target for TB vaccine development.<\/jats:p>","DOI":"10.3390\/pathogens14040370","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T07:49:02Z","timestamp":1744184942000},"page":"370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Silico Targeting and Immunological Profiling of PpiA in Mycobacterium tuberculosis: A Computational Approach"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3279-0671","authenticated-orcid":false,"given":"Mohammad J.","family":"Nasiri","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 19839-69411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lily","family":"Rogowski","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-1160","authenticated-orcid":false,"given":"Vishwanath","family":"Venketaraman","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024). Global Tuberculosis Report."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41572-024-00504-2","article-title":"Multidrug-resistant tuberculosis","volume":"10","author":"Dheda","year":"2024","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lv, H., Zhang, X., Zhang, X., Bai, J., You, S., Li, X., Li, S., Wang, Y., Zhang, W., and Xu, Y. (2024). Global prevalence and burden of multidrug-resistant tuberculosis from 1990 to 2019. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09079-5"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S90","DOI":"10.1016\/j.ijid.2022.02.043","article-title":"Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis","volume":"124","author":"Nasiri","year":"2022","journal-title":"Int. J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Nasiri, M.J., Lutfy, K., and Venketaraman, V. (2024). Challenges of Multidrug-Resistant Tuberculosis Meningitis: Current Treatments and the Role of Glutathione as an Adjunct Therapy. Vaccines, 12.","DOI":"10.3390\/vaccines12121397"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Seeberg, J. (2023). An epidemic of drug resistance: Tuberculosis in the twenty-first century. Pathogens, 12.","DOI":"10.3390\/pathogens12050652"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Nasiri, M.J., and Venketaraman, V. (2025). Advances in Host\u2013Pathogen Interactions in Tuberculosis: Emerging Strategies for Therapeutic Intervention. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041621"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/febs.17261","article-title":"Mycobacterial peptidyl prolyl isomerase A activates STING-TBK1-IRF3 signaling to promote IFN\u03b2 release in macrophages","volume":"292","author":"Sharma","year":"2025","journal-title":"FEBS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1093\/infdis\/jiab081","article-title":"Mycobacterium tuberculosis peptidyl prolyl isomerase a interacts with host integrin receptor to exacerbate disease progression","volume":"224","author":"Dubey","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pandey, S., Tripathi, D., Khubaib, M., Kumar, A., Sheikh, J.A., Sumanlatha, G., Ehtesham, N.Z., and Hasnain, S.E. (2017). Mycobacterium tuberculosis peptidyl-prolyl isomerases are immunogenic, alter cytokine profile and aid in intracellular survival. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00038"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pandey, S., Sharma, A., Tripathi, D., Kumar, A., Khubaib, M., Bhuwan, M., Chaudhuri, T.K., Hasnain, S.E., and Ehtesham, N.Z. (2016). Mycobacterium tuberculosis peptidyl-prolyl isomerases also exhibit chaperone like activity in-vitro and in-vivo. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150288"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"286","DOI":"10.24171\/j.phrp.2024.0026","article-title":"Novel prophylactic and therapeutic multi-epitope vaccine based on Ag85A, Ag85B, ESAT-6, and CFP-10 of Mycobacterium tuberculosis using an immunoinformatics approach","volume":"15","author":"Nugraha","year":"2024","journal-title":"Osong Public Health Res. Perspect."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/resp.13245","article-title":"Tuberculosis vaccines: Opportunities and challenges","volume":"23","author":"Zhu","year":"2018","journal-title":"Respirology"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ouyang, J., Guo, S., Hu, Z., Cao, T., Mou, J., Gu, X., Huang, C., and Liu, J. (2025). Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37Ra. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1430808"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Phogat, S., Yadav, J., Chaudhary, D., Jaiwal, R., and Jaiwal, P.K. (2025). Synthesis of an Adjuvant-Free Single Polypeptide-Based Tuberculosis Subunit Vaccine that Elicits In Vivo Immunogenicity in Rats. Molecular Biotechnology, Springer.","DOI":"10.1007\/s12033-025-01431-7"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.eimc.2017.10.015","article-title":"Pathogenesis of tuberculosis and other mycobacteriosis","volume":"36","author":"Cardona","year":"2018","journal-title":"Enferm. Infecc. Microbiol. Clin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.compbiolchem.2018.02.001","article-title":"The effect of in silico targeting Pseudomonas aeruginosa patatin-like protein D, for immunogenic administration","volume":"74","author":"Chirani","year":"2018","journal-title":"Comput. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.artmed.2018.12.010","article-title":"Antigenic: An improved prediction model of protective antigens","volume":"94","author":"Rahman","year":"2019","journal-title":"Artif. Intell. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101435","DOI":"10.1016\/j.imu.2023.101435","article-title":"An in silico approach to decipher immunogenic epitopes in Toxoplasma gondii GRA1 and GRA3","volume":"44","author":"Safari","year":"2024","journal-title":"Inform. Med. Unlocked"},{"key":"ref_20","first-page":"1320","article-title":"Bioinformatic analysis of small humanin like peptides using AlfaFold-2 and Expasy ProtParam","volume":"65","author":"Azimi","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gasteiger, E., Hoogland, C., Gattiker, A., Duvaud, S.e., Wilkins, M.R., Appel, R.D., and Bairoch, A. (2005). Protein Identification and Analysis Tools on the ExPASy Server, Springer.","DOI":"10.1385\/1-59259-890-0:571"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Morita, R., Shigeta, Y., and Harada, R. (2021). Comprehensive predictions of secondary structures for comparative analysis in different species. J. Struct. Biol., 213.","DOI":"10.1016\/j.jsb.2021.107735"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1002\/elps.200900140","article-title":"Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective","volume":"30","author":"Guex","year":"2009","journal-title":"Electrophoresis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"W252","DOI":"10.1093\/nar\/gku340","article-title":"SWISS-MODEL: Modelling protein tertiary and quaternary structure using evolutionary information","volume":"42","author":"Biasini","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: Homology modelling of protein structures and complexes","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jmgm.2014.04.001","article-title":"Computational study of protein secondary structure elements: Ramachandran plots revisited","volume":"50","author":"Carrascoza","year":"2014","journal-title":"J. Mol. Graph. Model."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1107\/S0907444909042073","article-title":"MolProbity: All-atom structure validation for macromolecular crystallography","volume":"66","author":"Chen","year":"2010","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","article-title":"MolProbity: More and better reference data for improved all-atom structure validation","volume":"27","author":"Williams","year":"2018","journal-title":"Protein Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W525","DOI":"10.1093\/nar\/gks438","article-title":"Immune epitope database analysis resource","volume":"40","author":"Kim","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D854","DOI":"10.1093\/nar\/gkp1004","article-title":"The immune epitope database 2.0","volume":"38","author":"Vita","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6760830","DOI":"10.1155\/2016\/6760830","article-title":"An introduction to B-cell epitope mapping and in silico epitope prediction","volume":"2016","author":"Potocnakova","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"D339","DOI":"10.1093\/nar\/gky1006","article-title":"The immune epitope database (IEDB): 2018 update","volume":"47","author":"Vita","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yun, J.S., Kim, A.R., Kim, S.M., Shin, E., Ha, S.J., Kim, D., and Jeong, H.S. (2024). In silico analysis for the development of multi-epitope vaccines against Mycobacterium tuberculosis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1474346"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Xu, J.-c., Hu, Z.-d., and Fan, X.-y. (2023). Advances in protein subunit vaccines against tuberculosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1238586"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kim, H., Choi, H.-G., and Shin, S.J. (2023). Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1193058"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Romano, M., Squeglia, F., Kramarska, E., Barra, G., Choi, H.-G., Kim, H.-J., Ruggiero, A., and Berisio, R. (2023). A structural view at vaccine development against M. tuberculosis. Cells, 12.","DOI":"10.3390\/cells12020317"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jurczak, M., and Druszczynska, M. (2025). Beyond Tuberculosis: The Surprising Immunological Benefits of the Bacillus Calmette\u2013Gu\u00e9rin (BCG) Vaccine in Infectious, Auto-Immune, and Inflammatory Diseases. Pathogens, 14.","DOI":"10.3390\/pathogens14020196"},{"key":"ref_39","unstructured":"WHO (2025, January 01). Global Tuberculosis Programme; New TB Vaccine Research. Available online: https:\/\/www.who.int\/teams\/global-tuberculosis-programme\/research-innovation\/vaccines?utm_source=chatgpt.com."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1038\/s41467-023-36789-2","article-title":"Safety and immunogenicity of a thermostable ID93+ GLA-SE tuberculosis vaccine candidate in healthy adults","volume":"14","author":"Sagawa","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4146","DOI":"10.1111\/febs.16369","article-title":"Secretory proteins of Mycobacterium tuberculosis and their roles in modulation of host immune responses: Focus on therapeutic targets","volume":"289","author":"Pal","year":"2022","journal-title":"FEBS J."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Passos, B.B., Ara\u00fajo-Pereira, M., Vinhaes, C.L., Amaral, E.P., and Andrade, B.B. (2024). The role of ESAT-6 in tuberculosis immunopathology. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1383098"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s11095-009-9995-y","article-title":"Rational design of multiple TB antigens TB10. 4 and TB10. 4-Ag85B as subunit vaccine candidates against Mycobacterium tuberculosis","volume":"27","author":"Shi","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kudryavtsev, I., Zinchenko, Y., Serebriakova, M., Akisheva, T., Rubinstein, A., Savchenko, A., Borisov, A., Belenjuk, V., Malkova, A., and Yablonskiy, P. (2023). A key role of cd8+ t cells in controlling of tuberculosis infection. Diagnostics, 13.","DOI":"10.3390\/diagnostics13182961"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Liu, H., Gui, X., Chen, S., Fu, W., Li, X., Xiao, T., Hou, J., and Jiang, T. (2022). Structural Variability of Lipoarabinomannan Modulates Innate Immune Responses within Infected Alveolar Epithelial Cells. Cells, 11.","DOI":"10.3390\/cells11030361"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1146\/annurev.cellbio.20.010403.114015","article-title":"Cell biology of Mycobacterium tuberculosis phagosome","volume":"20","author":"Vergne","year":"2004","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_47","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_48","doi-asserted-by":"crossref","unstructured":"Yun, J.-S., Shin, E., Lee, Y.-R., Lee, J.-A., Lee, H., Kim, J.-S., Shin, S.J., Ha, S.-J., Lee, S.-W., and Kim, D. (2025). Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1492268"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e37536","DOI":"10.1016\/j.heliyon.2024.e37536","article-title":"In silico design of Mycobacterium tuberculosis multi-epitope adhesin protein vaccines","volume":"10","author":"Pillay","year":"2024","journal-title":"Heliyon"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","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."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/4\/370\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:11:39Z","timestamp":1760029899000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/4\/370"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,9]]},"references-count":50,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["pathogens14040370"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14040370","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2025,4,9]]}}}