{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T22:39:38Z","timestamp":1769639978197,"version":"3.49.0"},"reference-count":45,"publisher":"IMR Press","issue":"7","license":[{"start":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T00:00:00Z","timestamp":1719964800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"crossref","award":["RSPD2024R568"],"award-info":[{"award-number":["RSPD2024R568"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Pneumocystis jirovecii is the most emerging life-threating health problem that causes acute and fatal pneumonia infection. It is rare and more contagious for patients with leukemia and immune-deficiency disorders. Until now there is no treatment available for this infection therefore, it is needed to develop any treatment against this pathogen. Methods: In this work, we used comparative proteomics, robust immune-informatics, and reverse vaccinology to create an mRNA vaccine against Pneumocystis jirovecii by targeting outer and transmembrane proteins. Using a comparative subtractive proteomic analysis of two Pneumocystis jirovecii proteomes, a distinct non-redundant Pneumocystis jirovecii (strain SE8) proteome was chosen. Seven Pneumocystis jirovecii transmembrane proteins were chosen from this proteome based on hydrophilicity, essentiality, virulence, antigenicity, pathway interaction, protein-protein network analysis, and allergenicity. Objective: The reverse vaccinology approach was used to predict the immunogenic and antigenic epitopes of major histocompatibility complex (MHC) I, II and B-cells from the selected proteins on the basis of their antigenicity, toxicity and allergenicity. These immunogenic epitopes were linked together to construct the mRNA-based vaccine. To enhance the immunogenicity, suitable adjuvant, linkers (GPGPG, KK, and CYY), and PRDRE sequences were used. Results: Through predictive modeling and confirmation via the Ramachandran plot, we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct\u2019s immunogenicity (GRAVY index: \u20130.271, instability index: 39.53, antigenicity: 1.0428). The physiochemical profiling of vaccine construct was predicted it an antigenic, efficient, and potential vaccine. Notably, strong interactions were observed between the vaccine construct and TLR-3\/TLR-4 (\u20131301.7 kcal\/mol-1 and \u20131374.7 kcal\/mol-1). Conclusions: The results predicted that mRNA-based vaccines trigger a cellular and humoral immune response, making the vaccine potential candidate against Pneumocystis jirovecii and it is more suitable for in-vitro analysis and validation to prove its effectiveness.<\/jats:p>","DOI":"10.31083\/j.fbl2907246","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T09:28:22Z","timestamp":1720171702000},"source":"Crossref","is-referenced-by-count":1,"title":["Designing an mRNA Vaccine against P. jirovecii Involved in Fatal Pneumonia Infections via Comparative Proteomics and Reverse Vaccinology Approaches"],"prefix":"10.31083","volume":"29","author":[{"given":"Muhammad","family":"Naveed","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, 54590 Lahore, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khizra","family":"Jabeen","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, 54590 Lahore, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq","family":"Aziz","sequence":"first","affiliation":[{"name":"Department of Agriculture University of Ioannina, 47100 Arta, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Saad","family":"Mughal","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, 54590 Lahore, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hammad","family":"Arif","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Faculty of Science and Technology, University of Central Punjab, 54590 Lahore, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Metab","family":"Alharbi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thamer H","family":"Albakeiri","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdullah F.","family":"Alasmari","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, 11451 Riyadh, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2024,7,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Salzer HJF, Sch\u00e4fer G, Hoenigl M, G\u00fcnther G, Hoffmann C, Kalsdorf B, et al. Clinical, Diagnostic, and Treatment Disparities between HIV-Infected and Non-HIV-Infected Immunocompromised Patients with Pneumocystis jirovecii Pneumonia. Respiration. 2018; 96: 52\u201365.","DOI":"10.1159\/000487713"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Menon AA, Berg DD, Brea EJ, Deutsch AJ, Kidia KK, Thurber EG, et al. A Case of COVID-19 and Pneumocystis jirovecii Coinfection. American Journal of Respiratory and Critical Care Medicine. 2020; 202: 136\u2013138.","DOI":"10.1164\/rccm.202003-0766LE"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Viceconte G, Buonomo AR, Lanzardo A, Pinchera B, Zappulo E, Scotto R, et al. Pneumocystis jirovecii pneumonia in an immunocompetent patient recovered from COVID-19. Infectious Diseases. 2021; 53: 382\u2013385.","DOI":"10.1080\/23744235.2021.1890331"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Ghembaza A, Vautier M, Cacoub P, Pourcher V, Saadoun D. Risk Factors and Prevention of Pneumocystis jirovecii Pneumonia in Patients With Autoimmune and Inflammatory Diseases. Chest. 2020; 158: 2323\u20132332.","DOI":"10.1016\/j.chest.2020.05.558"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Jeican II, Ini\u0219ca P, Gheban D, T\u0103b\u0103ran F, Alua\u0219 M, Trombitas V, et al. COVID-19 and Pneumocystis jirovecii Pulmonary Coinfection-The First Case Confirmed through Autopsy. Medicina. 2021; 57: 302.","DOI":"10.3390\/medicina57040302"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Coleman H, Snell LB, Simons R, Douthwaite ST, Lee MJ. Coronavirus disease 2019 and Pneumocystis jirovecii pneumonia: a diagnostic dilemma in HIV. AIDS. 2020; 34: 1258\u20131260.","DOI":"10.1097\/QAD.0000000000002571"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Bhat P, Noval M, Doub JB, Heil E. Concurrent COVID-19 and Pneumocystis jirovecii pneumonia in a severely immunocompromised 25-year-old patient. International Journal of Infectious Diseases. 2020; 99: 119\u2013121.","DOI":"10.1016\/j.ijid.2020.07.061"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Bateman M, Oladele R, Kolls JK. Diagnosing Pneumocystis jirovecii pneumonia: A review of current methods and novel approaches. Medical Mycology. 2020; 58: 1015\u20131028.","DOI":"10.1093\/mmy\/myaa024"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Basu A. In Silico Epitope-Based Vaccine Prediction against Fungal Infection Aspergillosis. Challenges. 2022; 13: 29.","DOI":"10.3390\/challe13020029"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Alanio A, Delli\u00e8re S, Voicu S, Bretagne S, M\u00e9garbane B. The presence of Pneumocystis jirovecii in critically ill patients with COVID-19. The Journal of Infection. 2021; 82: 84\u2013123.","DOI":"10.1016\/j.jinf.2020.10.034"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Jia L, Zhang Z, Bai Y, Du Q. VV-ECMO combined with prone position ventilation in the treatment of Pneumocystis jirovecii pneumonia: A case report. Medicine. 2022; 101: e28482.","DOI":"10.1097\/MD.0000000000028482"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Takeuchi K, Yakushijin Y. Pneumocystis jirovecii Pneumonia Prophylaxis for Cancer Patients during Chemotherapy. Pathogens. 2021; 10: 237.","DOI":"10.3390\/pathogens10020237"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Soltan MA, Eldeen MA, Elbassiouny N, Kamel HL, Abdelraheem KM, El-Gayyed HA, et al. In Silico Designing of a Multitope Vaccine against Rhizopus microsporus with Potential Activity against Other Mucormycosis Causing Fungi. Cells. 2021; 10: 3014.","DOI":"10.3390\/cells10113014"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Naveed M, Yaseen AR, Khalid H, Ali U, Rabaan AA, Garout M, et al. Execution and Design of an Anti HPIV-1 Vaccine with Multiple Epitopes Triggering Innate and Adaptive Immune Responses: An Immunoinformatic Approach. Vaccines. 2022; 10: 869.","DOI":"10.3390\/vaccines10060869"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Sanches RCO, Tiwari S, Ferreira LCG, Oliveira FM, Lopes MD, Passos MJF, et al. Immunoinformatics Design of Multi-Epitope Peptide-Based Vaccine Against Schistosoma mansoni Using Transmembrane Proteins as a Target. Frontiers in Immunology. 2021; 12: 621706.","DOI":"10.3389\/fimmu.2021.621706"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Akhtar N, Joshi A, Kaushik V, Kumar M, Mannan MAU. In-silico design of a multivalent epitope-based vaccine against Candida auris. Microbial Pathogenesis. 2021; 155: 104879.","DOI":"10.1016\/j.micpath.2021.104879"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Naveed M, Sheraz M, Amin A, Waseem M, Aziz T, Khan AA, et al. Designing a Novel Peptide-Based Multi-Epitope Vaccine to Evoke a Robust Immune Response against Pathogenic Multidrug-Resistant Providencia heimbachae. Vaccines. 2022; 10: 1300.","DOI":"10.3390\/vaccines10081300"},{"key":"ref18","unstructured":"UniProt Consortium. UniProt: the universal protein knowledgebase in 2021. Nucleic Acids Research. 2021; 49: D480\u2013D489."},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Huang LT, Wei KC, Wu CC, Chen CY, Wang JA. A lightweight BLASTP and its implementation on CUDA GPUs. The Journal of Supercomputing. 2021; 77: 322\u2013342.","DOI":"10.1007\/s11227-020-03267-1"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Wu JM, Liu YC, Chang DTH. SigUNet: signal peptide recognition based on semantic segmentation. BMC Bioinformatics. 2019; 20: 677.","DOI":"10.1186\/s12859-019-3245-z"},{"key":"ref21","unstructured":"Amber S, Mirza F J, Ali A, Zahid S. Computational Screening of Secretory Proteins With Brain-Specific Expression in Glioblastoma Multiforme. Reaserch Square. 2021. (preprint)"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Luo H, Lin Y, Liu T, Lai FL, Zhang CT, Gao F, et al. DEG 15, an update of the Database of Essential Genes that includes built-in analysis tools. Nucleic Acids Research. 2021; 49: D677\u2013D686.","DOI":"10.1093\/nar\/gkaa917"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Li YC, Lu YC. BLASTP-ACC: Parallel Architecture and Hardware Accelerator Design for BLAST-Based Protein Sequence Alignment. IEEE Transactions on Biomedical Circuits and Systems. 2019; 13: 1771\u20131782.","DOI":"10.1109\/TBCAS.2019.2943539"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Liu B, Zheng D, Zhou S, Chen L, Yang J. VFDB 2022: a general classification scheme for bacterial virulence factors. Nucleic Acids Research. 2022; 50: D912\u2013D917.","DOI":"10.1093\/nar\/gkab1107"},{"key":"ref25","unstructured":"Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. The Lancet. HIV. 2018; 5: e211\u2013e220."},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Raza A, Asif Rasheed M, Raza S, Tariq Navid M, Afzal A, Jamil F. Prediction and analysis of multi epitope based vaccine against Newcastle disease virus based on haemagglutinin neuraminidase protein. Saudi Journal of Biological Sciences. 2022; 29: 3006\u20133014.","DOI":"10.1016\/j.sjbs.2022.01.036"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Naveed M, Imran K, Mushtaq A, Mumtaz AS, Janjua HA, Khalid N. In silico functional and tumor suppressor role of hypothetical protein PCNXL2 with regulation of the Notch signaling pathway. RSC Advances. 2018; 8: 21414\u201321430.","DOI":"10.1039\/C8RA00589C"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Vita R, Overton JA, Peters B. Identification of errors in the IEDB using ontologies. Database. 2018; 2018: bay005.","DOI":"10.1093\/database\/bay005"},{"key":"ref29","unstructured":"Eslami G, Mehrani MJB, Lesani S, Askari V. Toxoplasma gondii proteins: development of bioinformatics analysis for vaccine design against toxoplasmosis. In Proceedings of the Bioinformatics of Genome Regulation and Structure\/Systems Biology (BGRS\/SB-2022). 2022; 787\u2013787."},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Chen P, Mao L, Nassis GP, Harmer P, Ainsworth BE, Li F. Coronavirus disease (COVID-19): The need to maintain regular physical activity while taking precautions. Journal of Sport and Health Science. 2020; 9: 103\u2013104.","DOI":"10.1016\/j.jshs.2020.02.001"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Khan T, Khan A, Ansari JK, Najmi MH, Wei DQ, Muhammad K, et al. Potential Immunogenic Activity of Computationally Designed mRNA- and Peptide-Based Prophylactic Vaccines against MERS, SARS-CoV, and SARS-CoV-2: A Reverse Vaccinology Approach. Molecules. 2022; 27: 2375.","DOI":"10.3390\/molecules27072375"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Sahay A, Piprodhe A, Pise M. In silico analysis and homology modeling of strictosidine synthase involved in alkaloid biosynthesis in catharanthus roseus. Journal, Genetic Engineering & Biotechnology. 2020; 18: 44.","DOI":"10.1186\/s43141-020-00049-3"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Buchan DWA, Jones DT. The PSIPRED Protein Analysis Workbench: 20 years on. Nucleic Acids Research. 2019; 47: W402\u2013W407.","DOI":"10.1093\/nar\/gkz297"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Porter KA, Padhorny D, Desta I, Ignatov M, Beglov D, Kotelnikov S, et al. Template-based modeling by ClusPro in CASP13 and the potential for using co-evolutionary information in docking. Proteins. 2019; 87: 1241\u20131248.","DOI":"10.1002\/prot.25808"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Arumugam S, Varamballi P. In-silico design of envelope based multi-epitope vaccine candidate against Kyasanur forest disease virus. Scientific Reports. 2021; 11: 17118.","DOI":"10.1038\/s41598-021-94488-8"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Khan T, Khan A, Ali SS, Ali S, Wei DQ. A computational perspective on the dynamic behaviour of recurrent drug resistance mutations in the pncA gene from Mycobacterium tuberculosis. RSC Advances. 2021; 11: 2476\u20132486.","DOI":"10.1039\/D0RA09326B"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Naveed M, Mughal MS, Jabeen K, Aziz T, Naz S, Nazir N, et al. Evaluation of the whole proteome to design a novel mRNA-based vaccine against multidrug-resistant Serratia marcescens. Frontiers in Microbiology. 2022; 13: 960285.","DOI":"10.3389\/fmicb.2022.960285"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Naveed M, Makhdoom SI, Ali U, Jabeen K, Aziz T, Khan AA, et al. Immunoinformatics Approach to Design Multi-Epitope-Based Vaccine against Machupo Virus Taking Viral Nucleocapsid as a Potential Candidate. Vaccines. 2022; 10: 1732.","DOI":"10.3390\/vaccines10101732"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Naveed M, Jabeen K, Aziz T, Mughual MS, Ul-Hassan J, Sheraz M, et al. Whole proteome analysis of MDR Klebsiella pneumoniae to identify mRNA and multiple epitope based vaccine targets against emerging nosocomial and lungs associated infections. Journal of Biomolecular Structure & Dynamics. 2023. (online ahead of print)","DOI":"10.1080\/07391102.2023.2293266"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Naveed M, Mehmood S, Aziz T, Hammad Arif M, Ali U, Nouroz F, et al. An mRNA-based reverse-vaccinology strategy to stimulate the immune response against Nipah virus in humans using fusion glycoproteins. Acta Biochimica Polonica. 2023; 70: 623\u2013631.","DOI":"10.18388\/abp.2020_6721"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Naveed M, Mahmood S, Aziz T, Azeem A, Hussain I, Waseem M, et al. Designing a novel chimeric multi-epitope vaccine subunit against Staphylococcus argenteus through artificial intelligence approach integrating pan-genome analysis, in vitro identification, and immunogenicity profiling. Journal of Biomolecular Structure & Dynamics. 2023; 1\u201316.","DOI":"10.1080\/07391102.2023.2256881"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Chukwudozie OS, Chukwuanukwu RC, Iroanya OO, Eze DM, Duru VC, Dele-Alimi TO, et al. Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In Silico Analysis. Journal of Immunology Research. 2020; 2020: 2837670.","DOI":"10.1155\/2020\/2837670"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Naveed M, Jabeen K, Naz R, Mughal MS, Rabaan AA, Bakhrebah MA, et al. Regulation of Host Immune Response against Enterobacter cloacae Proteins via Computational mRNA Vaccine Design through Transcriptional Modification. Microorganisms. 2022; 10: 1621.","DOI":"10.3390\/microorganisms10081621"},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Khan T, Muzaffar A, Shoaib RM, Khan A, Waheed Y, Wei DQ. Towards specie-specific ensemble vaccine candidates against mammarenaviruses using optimized structural vaccinology pipeline and molecular modelling approaches. Microbial Pathogenesis. 2022; 172: 105793.","DOI":"10.1016\/j.micpath.2022.105793"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Dunne DW, Shaw A, Bockenstedt LK, Allore HG, Chen S, Malawista SE, et al. Increased TLR4 expression and downstream cytokine production in immunosuppressed adults compared to non-immunosuppressed adults. PLoS ONE. 2010; 5: e11343.","DOI":"10.1371\/journal.pone.0011343"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/29\/7\/10.31083\/j.fbl2907246","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T14:07:20Z","timestamp":1732716440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/29\/7\/10.31083\/j.fbl2907246"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,3]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024]]}},"alternative-id":["S2768-6701(24)01215-2"],"URL":"https:\/\/doi.org\/10.31083\/j.fbl2907246","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,3]]},"article-number":"246"}}