Self-amplifying mRNA vaccine cocktail against Staphylococcus aureus: A multi-epitope immunoinformatics and structural...

Area of Science:

• Vaccinology
• Computational Biology
• Infectious Disease

Background:

• Staphylococcus aureus (S. aureus) poses a significant global health risk, with no licensed human vaccines currently available.
• There is an urgent need for effective non-antibiotic prophylactic strategies against invasive S. aureus infections.

Purpose of the Study:

• To design and computationally evaluate a bivalent self-amplifying mRNA (saRNA) vaccine cocktail targeting key S. aureus virulence factors (ClfA, Hly, SraP).
• To assess the safety, stability, and immunogenic potential of the candidate saRNA vaccines (SaBVax807 and SaTVax876) using a multi-method computational pipeline.

Main Methods:

• Utilized immunoinformatics, structural bioinformatics, and molecular simulations to identify immunodominant epitopes and design saRNA constructs.
• Performed molecular docking and dynamics simulations to validate antigen-antibody and antigen-HLA interactions.
• Conducted codon optimization for human cells and assessed vaccine candidates for safety, stability, and immunogenicity via in silico analyses.

Main Results:

• Successfully designed two saRNA vaccine candidates, SaBVax807 and SaTVax876, targeting S. aureus virulence antigens.
• Computational validation confirmed favorable binding interactions with antibodies and HLA alleles.
• In silico evaluations indicated favorable safety, structural stability, and predicted immunogenicity for the saRNA vaccine cocktail.

Conclusions:

• The designed saRNA vaccine cocktail demonstrates promising computational safety, stability, and immunogenic profiles against S. aureus.
• This study provides a strong in silico foundation for the development of novel S. aureus vaccines, guiding future preclinical and clinical research.