Objectives Current tuberculosis (TB) control strategies face limitations, such as low antibiotic treatment compliance and a rise in multidrug resistance. Furthermore, the lack of a safe and effective vaccine compounds these challenges. The limited efficacy of existing vaccines against TB underscores the urgency for innovative strategies, such as immunoinformatics. Consequently, this study aimed to design a targeted multi-epitope vaccine against TB infection utilizing an immunoinformatics approach.
Methods The multi-epitope vaccine targeted Ag85A, Ag85B, ESAT-6, and CFP-10 proteins. The design adopted various immunoinformatics tools for cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B lymphocyte (LBL) epitope prediction, the assessment of vaccine characteristics, structure modeling, population coverage analysis, disulfide engineering, solubility prediction, molecular docking/dynamics with toll-like receptors (TLRs), codon optimization/cloning, and immune simulation.
Results The multi-epitope vaccine, which was assembled using 12 CTL, 25 HTL, and 21 LBL epitopes associated with CpG adjuvants, showed promising characteristics. The immunoinformatics analysis confirmed the antigenicity, immunogenicity, and lack of allergenicity. Physicochemical evaluations indicated that the proteins were stable, thermostable, hydrophilic, and highly soluble. Docking simulations suggested high-affinity binding to TLRs, including TLR2, TLR4, and TLR9. In silico immune simulation predicted strong T cell (cytokine release) and B cell (immunoglobulin release) responses.
Conclusion This immunoinformatics-designed multi-epitope vaccine targeting Ag85A, Ag85B, ESAT-6, and CFP-10 proteins showed promising characteristics in terms of stability, immunogenicity, antigenicity, solubility, and predicted induction of humoral and adaptive immune responses. This suggests its potential as a prophylactic and therapeutic vaccine against TB.
Citations
Citations to this article as recorded by
Multidrug-resistant tuberculosis: a comprehensive review of pathogenesis, drug resistance, current treatment and future prospects Shweta Tiwari, Ankit Kumar Singh, Aarshu Acharya, Joyabroto Ghosh, Rashmi Prabha Singh Archives of Microbiology.2026;[Epub] CrossRef
Genome-Guided Mining and Integrated in Silico Approach Uncover Potential of Streptomyces Secondary Metabolites as Multi-Target Agents Against Candida albicans Biofilm Formation Ismail Ismail, Sylvia Utami Tunjung Pratiwi, Ema Damayanti, Jaka Widada, Ysrafil Ysrafil, Syamsu Nur, Abdul Halim Umar, Ira Handayani, Shanti Ratnakomala Network Modeling Analysis in Health Informatics an.2026;[Epub] CrossRef
Domain arrangement–driven immunogenicity of a computationally designed mRNA vaccine targeting PPE68, IrtA, and PE9 of Mycobacterium tuberculosis Theerawat Dobutr, Elena Stylianou, Helen McShane, Nawamin Pinpathomrat Scientific Reports.2026;[Epub] CrossRef
In silico framework for designing and validating a multi-stage subunit vaccine against Tuberculosis using reverse vaccinology approach Ayesha Liaqat, Kubra Dastgir, Muhammad Sajjad, Hafiz Muzzammel Rehman, Muhammad Waheed Akhtar, Masoud Foroutan PLOS One.2026; 21(8): e0356788. CrossRef
Computationally guided multi-epitope vaccine design targeting oncoprotein BZLF1, EBNA1, LMP1, and LMP2 for of EBV associated gastric cancer Elvin Delonio, Ysrafil Ysrafil, Herlina Eka Shinta, Sari Eka Pratiwi Journal of the Egyptian National Cancer Institute.2026;[Epub] CrossRef
Antigen 85B of Mycobacterium tuberculosis: From Immunodominant Antigen to Vaccine Candidate Vivek Chauhan, Gaytri Mahajan, Rakesh Kumar, Shrikanth S. Gadad, Subhash C. Chauhan, Chinnaswamy Jagannath, Subramanian Dhandayuthapani Vaccines.2026; 14(9): 811. CrossRef
Immunogenicity and protective efficacy of recombinant BCG expressing a multi-epitope vaccine against mycobacterium tuberculosis Xuan-ji Zhang, Jia-rui Luo, Ting-ting Tian, Juan Shi, Zheng-long Chai, Chuang Li, Si-yu Zhang, Tao Qu, Feng-bo Zhang, Yue-jie Zhu Frontiers in Cellular and Infection Microbiology.2026;[Epub] CrossRef
Computational systems immunology and multi-scale modeling for the design of a Multi-Epitope Vaccine (MEV) against emerging multidrug-resistant Klebsiella michiganensis Rasha Assad Assiri, Fayez M. Saleh, Sher Muhammad, Emmanuel O. Fenibo, Tonderayi Matambo International Microbiology.2026;[Epub] CrossRef
In Silico Targeting and Immunological Profiling of PpiA in Mycobacterium tuberculosis: A Computational Approach Mohammad J. Nasiri, Lily Rogowski, Vishwanath Venketaraman Pathogens.2025; 14(4): 370. CrossRef
New Advances in the Development and Design of Mycobacterium tuberculosis Vaccines: Construction and Validation of Multi-Epitope Vaccines for Tuberculosis Prevention Osnat Barazani, Thomas Erdos, Raafi Chowdhury, Gursimratpreet Kaur, Vishwanath Venketaraman Biology.2025; 14(4): 417. CrossRef
In-silico
epitope-based vaccines design: progress, challenges and the road ahead
Federica Cernuto, Avisa Maleki, Giulia Russo, Valentina Di Salvatore, Francesco Pappalardo Expert Opinion on Drug Discovery.2025; 20(12): 1701. CrossRef
Design of multi-epitope-based therapeutic vaccine candidates from HBc and HBx proteins of hepatitis B virus using reverse vaccinology and immunoinformatics approaches Patricia Gita Naully, Marselina Irasonia Tan, Husna Nugrahapraja, Aluicia Anita Artarini, Reza Aditama, Ernawati Arifin Giri-Rachman, Sheikh Arslan Sehgal PLOS ONE.2024; 19(12): e0313269. CrossRef
Objectives This study aimed to identify the optimal protein construction for designing a multi-epitope vaccine with both prophylactic and therapeutic effects against cervical cancer, utilizing an immunoinformatics approach. The construction process involved using capsid epitopes L1 and L2, as well as oncoproteins E5, E6, and E7 from human papillomavirus (HPV) types 16 and 18.
Methods An experimental in silico analysis with an immunoinformatics approach was used to develop 2 multi-epitope vaccine constructs (A and B). Further analysis was then conducted to compare the constructs and select the one with the highest potential against cervical cancer.
Results This study produced 2 antigenic, non-allergenic, and nontoxic multi-epitope vaccine constructs (A and B), which exhibited the ideal physicochemical properties for a vaccine. Further analysis revealed that construct B effectively induced both cellular and humoral immune responses.
Conclusion The multi-epitope vaccine construct B for HPV 16 and 18, designed for both prophylactic and therapeutic purposes, met the development criteria for a cervical cancer vaccine. However, these findings need to be validated through in vitro and in vivo experiments.
Citations
Citations to this article as recorded by
In-silico design and evaluation of a novel mRNA vaccine against human bocavirus 1: A neglected viral pathogen Aleeza Rubab, Asifa Sarfraz, Muhammad Umer Khan, Khaled Fahmi Fawy, Mohibullah Shah Computers in Biology and Medicine.2026; 200: 111344. CrossRef
Design of a Multi‐Epitope Vaccine Targeting α‐Synuclein for Parkinson's Disease Using Immunoinformatics Tools Tatiane Batista dos Santos, Helena de Almeida Cerqueira Kodel, Geniana da Silva Gomes, Tatiane de Oliveira Xavier Machado, Dalton Ferreira Matos, Rafael Junqueira Borges, Daniela Droppa‐Almeida, Margarete Zanardo Gomes Peptide Science.2026;[Epub] CrossRef
In-silico design of a multi-epitope vaccine candidate against Strongyloides stercoralis Yanick Aqua Stong Tangan, G. Takop Nchanji, Eric Ndumu, Abey Blessings Ayuk, Kongnyu Brandon Ngala, Melvis Berinyuy Dulandzev, Ntang Emmaculate Yaah, Lahngong Methodius Shinyuy, Cabirou Mounchili Shintouo, Bernis Neneyoh Yengo, Andreen Egbe Enowkpen, Mary BMC Infectious Diseases.2026;[Epub] CrossRef
The current landscape of therapeutic vaccination approaches for treatment of HPV-dependent malignancies Johanne Audouze-Chaud, Ann-Katrin Schlosser, Angelika B. Riemer npj Vaccines.2026;[Epub] CrossRef
Design of Multi‐Epitope DIVA‐Compatible Vaccine Candidate Against Canine Parvovirus 2 Shubham Sharma, Pratishtha Sharma, Ravindra Pal Mandar, Ram Kumar, Ashok Gaur, Mamta Gurjar, Rajesh Singathia, Braj Nandan Shringi, Sunita Choudhary, Amit Kumar Pandey Journal of Molecular Recognition.2026;[Epub] CrossRef
A bioinformatics pipeline for the design of a SART3-targeted cancer vaccine with enhanced immunogenicity Zeynab Bayat, Faezeh Mahdian-Khoo, Lida Samie, Amir Taherkhani Genomics & Informatics.2026;[Epub] CrossRef
Computational design of a novel chimeric multi-epitope vaccine against chlamydia trachomatis serovar a to prevent trachoma Muhammad Irsyad Amien, Bimanda Rizki Nurhidayat, Siti Ulfatur Rizqa, Siti Zahra Arfiani, Latiefah Noer Widiastuti, Galuh Prasasti Isbach Brazilian Journal of Microbiology.2026;[Epub] CrossRef
Computationally guided multi-epitope vaccine design targeting oncoprotein BZLF1, EBNA1, LMP1, and LMP2 for of EBV associated gastric cancer Elvin Delonio, Ysrafil Ysrafil, Herlina Eka Shinta, Sari Eka Pratiwi Journal of the Egyptian National Cancer Institute.2026;[Epub] CrossRef
Immunoinformatics Approach to Develop a Novel Chimeric L1/L2 Messenger RNA-based Vaccine Targeting a Broad Spectrum of Human Papillomavirus Species Nshimiyimana Sylvere, James Kimotho, Caroline Wangari Ngugi World's Veterinary Journal.2025; 15(2): 341. CrossRef
Multi-epitope vaccine construct against
Staphylococcus aureus
: insights from immunoinformatics and molecular dynamics simulations
K. Nachammai, P. Sangavi, K. Abishek, K. Langeswaran SAR and QSAR in Environmental Research.2025; 36(9): 795. CrossRef
Designing a Multi-Epitope Vaccine Against HPV 16, 18, 33, and 45 Targeting L1 and E7 Proteins: An Immunoinformatics Approach for Cervical Cancer Prevention and Therapy Md. Touki Tahamid Tusar, Niamul Haq, Hafizur Rahman Gazi, Raduyan Farazi, Mamun Bhuya, Md. Enamul Haque, Md. Golzar Hossain, Abdullah-Al-Jubayer Bioinformatics and Biology Insights.2025;[Epub] CrossRef
Modulation of epithelial homeostasis by HPV using Notch and Wnt June See Chong, John Doorbar Tumour Virus Research.2024; 18: 200297. CrossRef
First
Prev
