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Updated: Oct 12, 2025
Evaluating the Immune Response of a Nanoemulsion Adjuvant Vaccine Against Methicillin-Resistant Staphylococcus aureus MRSA Infection
Published on: September 1, 2023
Investigation of novel putative immunogenic targets against Staphylococcus aureus using a reverse vaccinology
Narjes Noori Goodarzi1, Negin Bolourchi2, Sepideh Fereshteh2
1Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Background:
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) strains is a significant public health concern. Considering the high morbidity and mortality of invasive S. aureus infections and multi-drug resistant strains, there is an urgent need for non-antibiotic immune-based approaches to cure these infections. Despite all efforts, vaccine candidates targeting S. aureus failed in human clinical trials, and no approved vaccine is available against this pathogen. Therefore, this study aimed to introduce suitable candidates for immunization against S. aureus using a comprehensive reverse vaccinology approach.
Methods:
In this study, we retrieved putative immunogenic targets from three different levels (literature review, automated reverse vaccinology, and manual reverse vaccinology) and evaluated them using several immunoinformatics analyses including antigenicity, allergenicity, PSI-BLAST to human proteome, physiochemical properties, B-cell, and T-cell epitopes. In the next step, the quartile method scoring was used to the shortlisted proteins. Finally, the molecular docking and immune simulation of immunogenic targets were performed.
Results:
This study presents 12 vaccine candidates, including three enzymatic proteins (WP_000222271.1, WP_001170274, and WP_000827736.1), three cell wall-associated proteins (WP_001125631.1, WP_000731642, and WP_000751265.1), two hemolysins (WP_000594517.1, and WP_000916697.1), one secretion involved protein (WP_000725226.1), one heme‑iron binding protein (WP_001041573.1), one superantigen like protein (WP_000668994.1) and one hypothetical proteins (WP_000737711.1).
Conclusion:
Through quartile scoring method, immune simulation and molecular docking, four promising targets including lytic transglycosylase IsaA, HlgA, secretory antigen precursor SsaA, and heme uptake protein IsdB were selected as the shortlisted proteins. It seems that a polarized immunization (Th1/Th17) response is needed for protection against this bacterium. An optimized formulation based on these putative immunogenic proteins and a wisely adjuvant selection may drive the immune system toward a full protection.
Insights
This study identified four promising vaccine candidates against multi-drug resistant Staphylococcus aureus (MRSA) using reverse vaccinology. These targets, including IsaA and HlgA, could form the basis of a new non-antibiotic immune-based therapy for S. aureus infections.
Area of Science:
- Microbiology
- Immunology
- Bioinformatics
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) pose significant public health threats due to high morbidity and mortality.
- Existing vaccine candidates for S. aureus have failed in clinical trials, highlighting the need for novel approaches.
- Non-antibiotic, immune-based strategies are urgently required to combat invasive S. aureus infections.
Purpose of the Study:
- To identify potential vaccine candidates against S. aureus using a comprehensive reverse vaccinology approach.
- To evaluate immunogenic targets through various in silico analyses.
- To select promising candidates for further development of S. aureus vaccines.
Main Methods:
- Retrieved putative immunogenic targets from literature review, automated, and manual reverse vaccinology.
- Performed immunoinformatics analyses including antigenicity, allergenicity, and epitope prediction.
- Utilized quartile scoring, molecular docking, and immune simulation to shortlist vaccine candidates.
Main Results:
- Identified 12 potential vaccine candidates, including enzymatic proteins, cell wall-associated proteins, hemolysins, and others.
- Selected four promising targets: lytic transglycosylase IsaA, HlgA, secretory antigen precursor SsaA, and heme uptake protein IsdB.
- Indicated that a polarized Th1/Th17 immune response is likely necessary for protection.
Conclusions:
- IsaA, HlgA, SsaA, and IsdB are promising candidates for developing a non-antibiotic vaccine against S. aureus.
- Optimized formulation and adjuvant selection are crucial for eliciting a protective immune response.
- This study provides a foundation for developing effective immune-based therapies against S. aureus infections.
