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Published in: BMC Infectious Diseases 1/2024

Open Access 01-12-2024 | Research

Development of a novel multi‑epitope vaccine against the pathogenic human polyomavirus V6/7 using reverse vaccinology

Authors: Reza Salahlou, Safar Farajnia, Nasrin Bargahi, Nasim Bakhtiyari, Faranak Elmi, Mehdi Shahgolzari, Steven Fiering, Srividhya Venkataraman

Published in: BMC Infectious Diseases | Issue 1/2024

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Abstract

Background

Human polyomaviruses contribute to human oncogenesis through persistent infections, but currently there is no effective preventive measure against the malignancies caused by this virus. Therefore, the development of a safe and effective vaccine against HPyV is of high priority.

Methods

First, the proteomes of 2 polyomavirus species (HPyV6 and HPyV7) were downloaded from the NCBI database for the selection of the target proteins. The epitope identification process focused on selecting proteins that were crucial, associated with virulence, present on the surface, antigenic, non-toxic, and non-homologous with the human proteome. Then, the immunoinformatic methods were used to identify cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes from the target antigens, which could be used to create epitope-based vaccine. The physicochemical features of the designed vaccine were predicted through various online servers. The binding pattern and stability between the vaccine candidate and Toll-like receptors were analyzed through molecular docking and molecular dynamics (MD) simulation, while the immunogenicity of the designed vaccines was assessed using immune simulation.

Results

Online tools were utilized to forecast the most optimal epitope from the immunogenic targets, including LTAg, VP1, and VP1 antigens of HPyV6 and HPyV7. A multi-epitope vaccine was developed by combining 10 CTL, 7 HTL, and 6 LBL epitopes with suitable linkers and adjuvant. The vaccine displayed 98.35% of the world's population coverage. The 3D model of the vaccine structure revealed that the majority of residues (87.7%) were located in favored regions of the Ramachandran plot. The evaluation of molecular docking and MD simulation revealed that the constructed vaccine exhibits a strong binding (-1414.0 kcal/mol) towards the host's TLR4. Moreover, the vaccine-TLR complexes remained stable throughout the dynamic conditions present in the natural environment. The immune simulation results demonstrated that the vaccine design had the capacity to elicit robust immune responses in the host.

Conclusion

The multi-parametric analysis revealed that the designed vaccine is capable of inducing sustained immunity against the selected polyomaviruses, although further in-vivo investigations are needed to verify its effectiveness.
Appendix
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Metadata
Title
Development of a novel multi‑epitope vaccine against the pathogenic human polyomavirus V6/7 using reverse vaccinology
Authors
Reza Salahlou
Safar Farajnia
Nasrin Bargahi
Nasim Bakhtiyari
Faranak Elmi
Mehdi Shahgolzari
Steven Fiering
Srividhya Venkataraman
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2024
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-024-09046-0

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