# Computational Design and Immunoinformatic Analysis of a Broad-Spectrum Edible Multi-Epitope Vaccine Against Salmonella for Poultry

## TL;DR

Scientists designed a low-cost edible vaccine using algae to fight Salmonella in poultry, aiming to reduce foodborne illness and antibiotic use.

## Contribution

A novel edible multi-epitope vaccine is computationally designed for Salmonella, using algae as a production platform and adjuvants to boost immune response.

## Key findings

- The LPS-adjuvanted vaccine construct binds strongly to Toll-like receptor 3, suggesting potent innate immune activation.
- Immune simulations predict durable humoral responses and effective antigen clearance.
- Codon optimization confirms high feasibility for algal expression, enabling scalable vaccine production.

## Abstract

This research has developed a promising edible vaccine to combat Salmonella infections in poultry, a major source of foodborne illness worldwide. Using advanced computational and immunoinformatic tools, the team designed two multi-epitope vaccine constructs targeting conserved proteins involved in bacterial adhesion and biofilm formation. The vaccines, engineered for expression in the microalga Chlorella vulgaris, incorporate immune-activating adjuvants—β-defensin-3 and lipopolysaccharide (LPS)—to stimulate robust immune responses. Structural modeling and molecular docking revealed that the LPS-based construct (Construct 2) binds strongly to Toll-like receptor 3, suggesting potent innate immune activation. Simulated immune responses showed effective IgM-to-IgG class switching and long-lasting antibody production, indicating strong protection potential. Codon optimization confirmed high expression feasibility in algae, paving the way for scalable, low-cost oral vaccine production. This innovation aligns with One Health principles, aiming to reduce antibiotic use in agriculture, enhance food safety, and mitigate antimicrobial resistance. Experimental trials are underway to validate the vaccine’s efficacy in live poultry.

Salmonellosis remains a persistent threat to global food safety and poultry productivity, compounded by rising antimicrobial resistance. Here, we report the in silico design and immunoinformatic validation of a broad-spectrum, edible multi-epitope vaccine targeting conserved adhesion and biofilm-associated proteins (FimH, AgfA, SefA, SefD, and MrkD) of Salmonella spp. Two constructs were engineered by integrating cytotoxic (CTL) and helper (HTL) epitopes with β-defensin-3 (HBD-3) or lipopolysaccharide (LPS) adjuvants, optimized for expression in Chlorella vulgaris. Structural modeling confirmed native-like folding (z-scores −2.58 and −5.22) and high stability indices. Molecular docking and dynamics revealed that the LPS-adjuvanted construct (Construct 2) forms a highly stable complex with Toll-like receptor 3 (HADDOCK score −63.4; desolvation energy −50.2 kcal/mol), indicating potent innate immune activation. Immune simulations predicted strong IgM-to-IgG class switching and durable humoral responses, consistent with effective antigen clearance. Codon optimization achieved high adaptability for algal expression (CAI = 0.93; GC ≈ 65%), supporting scalable microalgae-based production. Compared with current parenteral vaccines, offering a low-cost, non-invasive way to curb Salmonella in poultry, this edible vaccine platform reduces dependence on antibiotics. Our approach, which combines computational vaccinology with a safe-by-design sustainable biomanufacturing perspective, outlines a One Health framework for advancing antimicrobial stewardship and food safety.