ORIGINAL RESEARCH article
Front. Bioinform.
Sec. Drug Discovery in Bioinformatics
IN SILICO AND IMMUNOINFORMATIC APPROACH TO DESIGN A MULTI-EPITOPE MRNA VACCINE TARGETING ALL MAJOR HUMAN-INFECTING GENOTYPES OF HEPATITIS E VIRUS
- MM
Maham Mehrangaze Khonza 1
- ZS
Zain Saeed 2
- ZJ
Zohra Jabeen 1
- WA
Wafaa Arab 3
- SK
Sehrish Kakakhel 4
- MY
Maham Yamin 5
- MG
MAZEN GHAITH 6
- AZ
Ali Zohaib 7
- AJ
Aneela Javed 1
- RH
Rwaa H. Abdulal 8
1. National University of Sciences and Technology, Islamabad, Pakistan
2. National University of Science and Technology, Islamabad, Pakistan
3. King Abdulaziz University, Jeddah, Saudi Arabia
4. Abdul Wali Khan University Mardan, Mardan, Pakistan
5. The University of Melbourne, Parkville, Australia
6. Umm Al-Qura University, Makkah, Saudi Arabia
7. King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
8. King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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Abstract
Background: Hepatitis E virus (HEV) is one of the major causative agents of acute and chronic hepatitis among humans across the globe and is linked to severe outcomes in immunocompromised individuals and pregnant women. Despite its substantial global burden, only one vaccine is licensed (in China and Pakistan) and has limited genotype coverage. There is an urgent need for a safe and broadly protective vaccine against HEV. Methods: In this study, amino acid sequences of ORF2 capsid protein of HEV genotypes 1-4 homologues were analyzed to generate a consensus sequence. Conserved epitopes were screened for antigenicity, allergenicity, toxicity, IFN-γ induction and human non-homology. Selected CTL, B-Cell and HTL epitopes were assembled in to a multi-epitope mRNA constructed with β-defensin adjuvant, correct linkers, and regulatory elements [Kozak, tPA, MITD, and globin UTRs]. The construct was structurally modelled, refined, and validated, and docked with the TLR7 receptor, followed by normal mode analysis and immune simulations. Results: The vaccine construct showed high antigenicity scored (≥ 0.7 - 0.8), non-allergenicity, stability, and strong epitope conservancy (75% - 90%). Docking and simulations indicated stable receptor binding, strong cellular and humoral immune responses with persistent Band T-cell interactions and enhanced cytokine levels. Strong population coverage (>99%) was also predicted. Conclusion: The designed multi-epitope mRNA vaccine shows strong in silico immunogenicity and stability against HEV. These results support further experimental validation to assess its translational potential.
Summary
Keywords
Hepatitis E virus, immunoinformatics, mRNA vaccine, Multi-epitope mRNA Vaccine, reverse vaccinology, Vaccine Design, Viral genotypes
Received
29 June 2026
Accepted
11 August 2026
Copyright
© 2026 Khonza, Saeed, Jabeen, Arab, Kakakhel, Yamin, GHAITH, Zohaib, Javed and Abdulal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Ali Zohaib; Aneela Javed; Rwaa H. Abdulal
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.