Work

In silico design and experimental validation of a multi-epitope vaccine candidate against Helicobacter hepaticus associated chronic liver inflammation

Year: 2026

Type: article

Abstract: Background Helicobacter hepaticus is an emerging enterohepatic pathogen associated with chronic gastrointestinal and hepatic inflammatory disorders. Despite its clinical relevance, effective vaccination strategies remain unavailable due to antigenic variability, immune evasion, and limited induction of durable cellular immunity. Methods An integrated reverse vaccinology and experimental validation approach was employed to design a multi-epitope vaccine against H. hepaticus . Two conserved outer membrane proteins, BamA and an organic solvent tolerance protein, were selected based on antigenicity, surface exposure, and safety profiling. Immunodominant cytotoxic and helper T-cell epitopes were predicted, screened for immunogenicity, allergenicity, and toxicity, and assembled into a rationally designed construct incorporating human β-defensin-3 as an adjuvant. Structural modeling, conformational B-cell epitope mapping, molecular docking, molecular dynamics simulations, and in silico immune simulations were performed. The construct was recombinantly expressed in Escherichia coli and evaluated through biophysical, antibacterial, and immunological assays. Results The vaccine candidate exhibited favorable physicochemical properties, structural stability, and strong binding affinity toward Toll-like receptor 2. In silico immune simulations predicted robust Th1-biased immune responses with effective memory formation. Recombinant expression yielded a soluble, monodisperse protein. Functional assays demonstrated significant inhibition of H. hepaticus growth and host cell adhesion. In vitro immunogenicity studies revealed strong peripheral blood mononuclear cell proliferation, enhanced CD4 + and CD8 + T-cell activation, elevated Th1 cytokine secretion, and antigen-specific antibody production. Conclusion The proposed multi-epitope vaccine candidate induces coordinated innate and adaptive immune responses and exhibits promising antibacterial activity against H. hepaticus . This study provides a comprehensive and translational framework for epitope-based vaccine development and supports further in vivo evaluation of the candidate vaccine.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1799290

Authors: Liangliang Weng, Zhang Huijie, Ni Man, Liu Yang, Min Cao

Institutions: Wenzhou Medical University, Quzhou City People's Hospital, Xuzhou Medical College

Language: English

Topic: vaccines and immunoinformatics approaches

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801