Immunoinformatics based designing and simulation of multi-epitope vaccine against multi-drug resistant Stenotrophomonas maltophilia

Stenotrophomonas maltophilia is a leading opportunistic bacterium responsible for a variety of nosocomial infections in humans, particularly among immunocompromised population. Therapeutic options are limited due to pathogen profound resistance and lack of a licensed vaccine. To address this problem, an integrative computational strategy including subtractive proteomics, immuno-informatics, molecular dynamics simulation, and immune response simulation is employed herein to design an efficacious multi-epitope vaccine against S. maltophilia. Four putative antigenic membrane proteins: Methylaccepting chemotaxis, Putative outer-membrane usher, Fimbrial biogenesis outer-membrane usher, and Flagellin unveiled as potential vaccine targets through subtractive proteomics. These proteins are non-human homologous, virulent, and crucial for pathogen survival. Stringent immunoinformatics analysis revealed two non-allergenic B-cell derived T-cell epitopes from FimD, capable of eliciting both humoral and cellular immunity. Multi-epitope construct is designed by stitching preferred peptides with immunogenicity enhancer adjuvant and linkers. Vaccine construct meets the criteria of physiochemistry, immunogenicity, and non-allergenicity. Docked pose of construct-TLR4 complex validated and subjected to molecular dynamics simulations to explore its dynamic behaviour in an aqueous environment. Structural changes were observed in complex, while vaccine construct remained exposed to TLR4 receptor surface. Immune simulations predicted significant T and B-cells proliferation, induced macrophage activity, with increased production of INF-gamma, and IL-2 in response to the antigen. All these analyses predicted that this designed vaccine could provoke host robust immune responses and could serve as a protective antigen against S. maltophilia. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study designed a multi-epitope vaccine against S. maltophilia using an integrative computational strategy, identified potential antigenic membrane proteins through subtractive proteomics and immunoinformatics analysis, designed vaccine construct by stitching preferred peptides, validated the docked pose of construct-TLR4 complex, and explored its dynamic behavior through molecular dynamics simulations. The immune simulations predicted robust immune responses, indicating the potential of this designed vaccine as a protective antigen against S. maltophilia.