Evaluation of the whole proteome to design a novel mRNA-based vaccine against multidrug-resistant Serratia marcescens

Abstract

Serratia marcescens, a Gram-negative bacterium, is one of the known disease-causing pathogens. It is resistant to ampicillin, macrolides, cephalosporins, cefotaxime, and ceftazidime. The only antibiotic that has been proven to be effective against S. marcescens is gentamicin. By causing epigenetic alterations, bacteria can also become resistant to all antibiotics. Many epigenetically related proteins were studied, and four proteins were selected in this regard for epitope evaluation and their subsequent use in the development of a messenger ribonucleic acid (mRNA) vaccine. A series of immune-informatics tools used to build this mRNA vaccine elicited cellular and humoral immunity. Molecular docking between epitopes and alleles of the major histocompatibility complex (MHC) was performed. The vaccine was developed using 37 epitopes, an adjuvant that is a TLR-4 agonist known as resuscitation-promoting factor E (RpfE), subcellular trafficking structures, secretion boosters, and linkers. This proposed architecture was found to cover 99.6% of the population during testing. During testing, it was proven that it was both effective and safe. To confirm our idea, we performed an in silico immunological simulation of vaccination. The codon was also optimized to ensure that the mRNA reached the cytoplasm of a human host and underwent efficient translation. TLR-4 and TLR-3 were also docked against the secondary and tertiary structures of the vaccine peptide. Furthermore, the vaccine's stability was confirmed by molecular dynamics simulation. In summary, this vaccine construct can be a potential candidate against S. marcescens and is suitable for in vitro analyses to validate its effectiveness.