Development of a chimeric multi-epitope vaccine targeting surface-exposed proteins of Chlamydia psittaci through...

Chlamydia psittaci is an obligate intracellular zoonotic pathogen that causes psittacosis and severe respiratory illness in humans. Despite its clinical importance, no licensed vaccine is currently available, and antibiotic treatment may not provide long-term protection or prevent recurrent infection. To address this challenge, a computational strategy integrating structural vaccinology and immunoinformatics was used to design a multi-epitope vaccine targeting the major outer membrane porin and the virulence-associated pGP3-D protein of C. psittaci. Cytotoxic T-cell and helper T-cell epitopes were identified and screened to select antigenic candidates. The selected epitopes were joined using linker sequences together with β-defensin-3 and PADRE. The vaccine construct was evaluated using physicochemical analysis, three-dimensional structural modeling, interaction analysis with TLR2, a 500 ns molecular dynamics simulation, MM-GBSA binding free-energy analysis, immune simulation, and in silico cloning. The designed vaccine was predicted to possess favorable antigenicity, a non-allergenic profile, suitable physicochemical properties, and a global population coverage of 92.15%. Computational analyses suggested stable interaction with TLR2 and indicated structural stability of the vaccine-receptor complex during the simulation. Immune simulation predicted increased IgG levels, memory B-cell formation, activation of CD8⁺ T lymphocytes, and a cytokine profile consistent with Th1-type immune responses. These findings suggest that the proposed construct represents a computationally designed multi-epitope vaccine candidate that requires further evaluation through experimental studies to determine its safety, immunogenicity, and protective efficacy against C. psittaci.