Designing a Tetravalent mRNA Vaccine for Scarlet Fever: Integrating Machine Learning and Reverse Vaccinology

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Abstract
Scarlet fever, commonly referred to as sandpaper rash, is a prevalent infection caused by the bacterium Streptococcus pyogenes, which is part of the Group A Streptococcus (GAS) family of gram-positive cocci. This infection affects both adults and children worldwide. This study focused on designing a tetravalent modified nucleotide mRNA vaccine using machine learning and reverse vaccinology techniques. The vaccine development focuses on three critical proteins: C5a peptidase, M protein, and streptolysin O. These proteins play significant roles in the pathogenesis of Streptococcus pyogenes and are key targets for inducing a robust immune response. Methods:. Our study involved extensive profiling for potential vaccine targets, which included three types of epitopes, namely B-cell, CTL, and HTL. The process we undertook in the choice of these epitopes was based on a range of significant criteria such as the ones with high antigenicity that ensure the immune system is able to recognize and respond to the vaccine; the ones with low toxicity that would be used to reduce the side effects, and those of no allergenicity to avoid cases of allergic reactions among vaccinated individuals. To further evaluate the interactions between the identified T-cell epitopes and their corresponding human leukocyte antigen (HLA) alleles, we employed molecular docking studies. Results: The results indicated promising binding affinities, suggesting that these epitopes are likely to elicit strong T-cell responses.Notably, the docking analysis revealed a binding energy of -818.5 kcal/mol for the peptide NTTNRHYSL with HLA-B08:01, and -776.5 kcal/mol for RTYPAALQL with HLA-A32:01. These studies provided insights into how well the epitopes bind to specific HLA molecules, which is vital for T-cell recognition and activation. Conclusion: These two peptides, exhibiting optimal binding affinity and stability, are promising candidates for advancing the development of next-generation mRNA vaccines. Further validation will be conducted through in vitro analyses to confirm their ability to elicit an immune response.

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