Immunoinformatic-based design of a multi-epitope subunit vaccine against Ruminococcus torques using subtractive...

Area of Science:

• Microbiology
• Immunology
• Bioinformatics

Background:

• Ruminococcus torques is an anaerobic, Gram-positive gut bacterium implicated in gastrointestinal diseases like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).
• This bacterium's mucolytic activity compromises intestinal barrier integrity, contributing to dysbiosis and pathogenicity.
• Emerging evidence links R. torques to extraintestinal infections, including pneumonia and bacteremia, particularly in immunocompromised individuals, underscoring the need for effective prophylaxis.

Purpose of the Study:

• To design a candidate multi-epitope vaccine against Ruminococcus torques using bioinformatics and immunoinformatics strategies.
• To identify potent B- and T-cell epitopes from the R. torques proteome with high antigenicity, non-allergenicity, and non-toxicity.
• To computationally validate the vaccine construct's structure, receptor binding, and expression potential.

Main Methods:

• Proteomic analysis of Ruminococcus torques strain ATCC 27,756 to identify target proteins (FtsX, single-stranded DNA binding protein, FtsW).
• In silico selection and linkage of B- and T-cell epitopes using spacers and an adjuvant.
• Computational modeling, refinement, validation, molecular docking against TLR4, and molecular dynamics simulation of the vaccine construct.
• In silico cloning to assess GC content and Codon Adaptation Index (CAI) for expression potential.

Main Results:

• Identification of key R. torques proteins and selection of high-quality epitopes for vaccine design.
• Successful in silico construction, structural modeling, and validation of a multi-epitope vaccine candidate.
• Demonstrated potential binding affinity to Toll-like receptor 4 (TLR4) and stability via molecular dynamics simulations.
• In silico cloning indicated high expression potential with a GC content of 49.29% and a CAI of 0.875.

Conclusions:

• The study computationally designed a promising multi-epitope vaccine candidate against Ruminococcus torques.
• In silico analyses suggest favorable antigenicity, non-toxicity, and high expression potential for the proposed vaccine.
• Experimental validation is crucial to confirm the immunogenicity and protective efficacy of this novel vaccine strategy against R. torques infections.