Designing a multi-epitope vaccine against Mycobacteroides abscessus by pangenome-reverse vaccinology

Abstract

Mycobacteroides abscessus (Previously Mycobacterium abscessus) is an emerging microorganism of the newly defined genera Mycobacteroides that causes mainly skin and tissue diseases in humans. The recent availability of total 34 fully sequenced genomes of different strains belonging to this species has provided an opportunity to utilize this genomics data to gain novel insights and guide the development of specific antimicrobial therapies. In the present study, we collected collectively 34 complete genome sequences of M. abscessus from the NCBI GenBank database. Pangenome analysis was conducted on these genomes to understand the genetic diversity and to obtain proteins associated with its core genome. These core proteins were then subjected to various subtractive filters to identify potential antigenic targets that were subjected to multi-epitope vaccine design. Our analysis projected the open pangenome of M. abscessus containing 3443 core genes. After applying various stepwise filtration steps on the core proteins, a total of four potential antigenic targets were identified. Utilizing their constituent CD4 and CD8 T-cell epitopes, a multi-epitope based subunit vaccine was computationally designed. Sequence-based analysis as well as structural characterization revealed the immunological effectiveness of this designed vaccine. Further molecular docking, molecular dynamics simulation and binding free energy estimation with Toll-like receptor 2 indicated strong structural associations of the vaccine with the immune receptor. The promising results are encouraging and need to be validated by additional wet laboratory studies for confirmation.

Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach

“…Bacterial pan-genome analysis is a bioinformatics approach mainly used for the retrieval of core, unique and accessory genes. Herein, the bacterial pan-genome analysis was considered to investigate the pan-genome of the pathogen [19]. Through the one-click analysis technique of the BPGA tool [43], all 14 strains of P. rettgeri were analyzed for core genome (conserved), along with accessory genes (dispensable) and unique genes (strain-specific genes) [44].…”

“…The 3D structure of the vaccine construct was modeled using the 3Dpro tool to predict the most stable vaccine structure, as it is essential for molecular recognition. The 3D structure was checked to ensure the construct's stability and durability [19].…”

“…Pasteur's rule of vaccines led to the development of the BCG vaccine against Mycobacterium tuberculosis [17], along with the vaccine against mumps, measles, and rubella [18]. However, such vaccinology is a failure for pathogens that are unable to be cultured or grown in the laboratory [19]. In addition, culture-based developed vaccines exhibit antigenic variability [20].…”

Virulence Mechanisms of Mycobacterium abscessus: Current Knowledge and Implications for Vaccine Design

“…There is also an extensive range of protein pathway mapping, MHC-II binding prediction, and epitope mapping software currently available which provides greater insight into those proteins likely to yield immunogenic vaccine candidates ( Heinson et al, 2015 ). The reverse vaccinology approach has most recently been used to identify potential VFs and therapeutic targets of M. abscessus by development of a novel hierarchical approach; the development of such workflows is beneficial because they may be applied to other pathogens in future ( Dar et al, 2021 ). There is also enormous advantage in a synergistic approach using wet-lab based and in silico techniques as a starting point for vaccine candidate identification, as this is based upon the confirmed proteome or secretome of different species.…”

Pan-Genome Reverse Vaccinology Approach for the Design of Multi-Epitope Vaccine Construct against Escherichia albertii

“…In order to prioritize and build vaccine targets against various infectious pathogens, the reverse vaccinology approach has been extensively used, e.g., against Yellow fever [ 12 ], Mycobacteroides abscessus [ 13 ], Acinetobacter baumannii [ 14 ] infection. In the current study, we applied pan-genomic analysis to figure out the strain’s accessory, core, and unique genome.…”