Multi-epitope chimeric vaccine designing and novel drug targets prioritization against multi-drug resistant Staphylococcus pseudintermedius

Abstract

Biofilm synthesizing multi-drug resistant Staphylococcus pseudintermedius bacteria has been recognized as the human infectious agent. It has been detected in the diseases of skin, ear, and postoperative infections. Its infections are becoming a major health problem due to its multi-drug resistance capabilities. However, no commercial vaccine for the treatment of its infections is currently available in the market. Here we employed the subtractive proteomics and reverse vaccinology approach to determine the potential novel drug and vaccine targets against S. pseudintermedius infections in humans. After screening the core-proteome of the 39 complete genomes of S. pseudintermedius, 2 metabolic pathways dependent and 34 independent proteins were determined as novel potential drug targets. Two proteins were found and used as potential candidates for designing the chimeric vaccine constructs. Depending on the properties such as antigenicity, toxicity and solubility, multi-epitope based vaccines constructs were designed. For immunogenicity enhancement, different specific sequences like linkers, PADRE sequences and molecular adjuvants were added. Molecular docking and molecular dynamic simulation analyses were performed to evaluate the prioritized vaccine construct’s interactions with human immune cells HLA and TLR4. Finally, the cloning and expression ability of the vaccine construct was determined in the bacterial cloning system and human body immune response was predicted through immune simulation analysis. In conclusion, this study proposed the potential drug and vaccine targets and also designed a chimera vaccine to be tested and validated against infectious S. pseudintermedius species.

Computer-aided genomic data analysis of drug-resistant Neisseria gonorrhoeae for the Identification of alternative therapeutic targets

“…It is therefore helpful to predict T-cell epitopes for effective vaccine construct prioritization. Cytotoxic or helper T-cells are stimulated by MHC binding molecule (Jaan et al, 2022). Immune Epitope Database server (IEDB) (Fleri et al, 2017b) was employed for the prediction of MHC binding epitopes with criteria of lower percentile rank i.e.…”

“…Linear B-Cell epitope prediction was performed by BCPreds, FBCPred and BepiPred (El-Manzalawy et al, 2008) servers. Prioritization was given in the downstream analyses to B-cell, MHC-1 and MHC-2 overlapping epitopes (Jaan et al, 2022).…”

“…PatchDock is a shape complimentary algorithmic tool to evaluate structural interactions of novel vaccine targets with the ligands (Jaan et al, 2022). Two final vaccine constructs were docked with six commonly occurring HLA alleles by PatchDock server to exhibit HLA-Peptide interactions (Solanki and Tiwari, 2018).…”

“…DEG analysis showed that 1 protein in KEGG dependent and 79 proteins in KEGG independent pathway were essential for the bacterial survival. Moreover, the pathogenic capacity of bacteria to overwhelm the host is enhanced by the virulence factors (Shah et al, 2021;Jaan et al, 2022). Thus, virulence factor analysis was performed by VFDB where 1 and 28 proteins were found to be virulent as in KEGG pathways dependent and independent, respectively.…”

“…Structure-function association among antigen and antibody can be predicted by conformational Bcell epitope prediction. Due to unavailability of 3D structures, conformational B-cell epitope cannot be predicted (Shah et al, 2021;Jaan et al, 2022).…”