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.

Background: Zika virus (ZIKV) is an arbovirus that belongs to family Flaviviridae. The virus has emerged as a global threat and no FDA approved vaccine is available, so an efficient vaccine needs to be designed in order to prevent the infection. Computationally designed vaccines can be used for broad-spectrum therapeutics as they can evoke response against viral infections. In the current study, we have predicted antigenic promiscuous T cell epitopes from Zika virus polyprotein using a range of immune-informatics tools and servers.Methods: A total of 238 polyprotein sequences derived from 238 complete genomes were retrieved using NIAID Virus Pathogen Resource and multiple aligned. Using a consensus sequence, the promiscuous CD8-T cell epitopes were predicted from Propred I and CTLPred and their binding affinities were determined by NetMHC4.0. CD4-T cell epitopes were predicted using ProPred and the binding affinities were determined by MHCPred. Antigenicity score and Immunogenicity score was determined from Vaxijen 2.0 and IEDB immunogenicity tool. Homology was found by pBLAST.Results: Among 78 predicted HLA-I binding epitopes, 19 highly antigenic, immunogenic and high-affinity epitopes are prioritized among which 15 are novel vaccine candidates. However, 66 strong HLA-II interacting T cell epitopes are pooled out from 70 predicted epitopes. Among the shortlisted CD4-T cell epitopes 56 epitopes are novel. Conclusion:Epitope-based vaccines are robust and promising candidates against bacterial and viral infections. The predicted epitopes can serve as potential vaccine candidates. Our study shows promising epitopes that can be used to generate stimulate active immune responses in the majority of the human population around the world, However, our results need validation through experimental studies for confirmation. PeerJ Preprints Abstract:Background:

Respiratory syncytial virus (RSV) usually causes respiratory tract infections of upper airways in infants and young children. Despite recent medical advances, no approved vaccine is available to control RSV infections. Therefore, we conducted an immunoinformatics study to design and evaluate a potential multi-epitope vaccine against RSV. Sequence-based analyses of the glycoproteins F and G revealed a total of eight CD8 T-cell and three CD4 T-cell epitopes after considering antigenicity, binding affinity and other parameters. Molecular docking analysis confirmed that these T-cell epitopes developed strong structural associations with HLA allele(s). By integrating these prioritized epitopes with linkers and a cholera toxin-derived adjuvant, a multi-epitope vaccine was designed. The developed vaccine was found to be stable, non-allergenic, flexible and antigenic. Molecular docking analysis revealed a striking mean HADDOCK score (−143.3) of top-ranked vaccine-TLR cluster and a Gibbs free energy change (ΔG) value of −11.3 kcal mol−1. As per computational immune simulation results, the vaccine generated a high titer of antibodies (especially IgM) and effector T-cells. Also, codon optimization and in silico cloning ensured the increased expression of vaccine in Escherichia coli. Altogether, we anticipate that the multi-epitope vaccine reported in this study will stimulate humoral and cellular responses against RSV infection, subject to follow-up experimental validation.

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