Designing a multi-epitope vaccine against Mycobacteroides abscessus by pangenome-reverse vaccinology. 2021

Hamza Arshad Dar, and Saba Ismail, and Yasir Waheed, and Sajjad Ahmad, and Zubia Jamil, and Hafsa Aziz, and Helal F Hetta, and Khalid Muhammad
Foundation University Medical College, Foundation University Islamabad, DHA-I, Islamabad, 44000, Pakistan.

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.

UI MeSH Term Description Entries
D009165 Mycobacterium Infections, Nontuberculous Infections with nontuberculous mycobacteria (atypical mycobacteria): M. kansasii, M. marinum, M. scrofulaceum, M. flavescens, M. gordonae, M. obuense, M. gilvum, M. duvali, M. szulgai, M. intracellulare (see MYCOBACTERIUM AVIUM COMPLEX;), M. xenopi (littorale), M. ulcerans, M. buruli, M. terrae, M. fortuitum (minetti, giae), M. chelonae, M. leprae. Mycobacterium Infections, Atypical,Atypical Mycobacterial Infection, Disseminated,Atypical Mycobacterial Infection, Familial Disseminated,Atypical Mycobacteriosis, Familial,Atypical Mycobacteriosis, Familial Disseminated,Atypical Mycobacterium Infections,Infections, Atypical Mycobacterium,Mycobacterium abscessus Infection,Atypical Mycobacterium Infection,Familial Atypical Mycobacterioses,Familial Atypical Mycobacteriosis,Infection, Mycobacterium abscessus,Infections, Mycobacterium abscessus,Mycobacterioses, Familial Atypical,Mycobacteriosis, Familial Atypical,Mycobacterium Infection, Atypical,Mycobacterium Infection, Nontuberculous,Mycobacterium abscessus Infections,Nontuberculous Mycobacterium Infection,Nontuberculous Mycobacterium Infections
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073358 Mycobacterium abscessus A rapidly growing non-tuberculous environmental mycobacterium causing OPPORTUNISTIC INFECTION that infects the skin and subcutaneous tissues. It is associated with HEALTH CARE ASSOCIATED INFECTION and causes serious lung infections in persons with various chronic lung diseases. Mycobacteroides abscessus,Mycobacteroides abscessus subsp. abscessus,Mycobacteroides abscessus subsp. massiliense,Mycobacterium abscessus Complex,Mycobacterium abscessus abscessus,Mycobacterium abscessus bolletii,Mycobacterium abscessus subsp. abscessus,Mycobacterium abscessus subsp. bolletii,Mycobacterium abscessus subspecies abscessus,Mycobacterium abscessus subspecies bolletii,Mycobacterium bolletii,Mycobacterium chelonae abscessus,Mycobacterium massiliense
D000078782 Vaccinology Branch of medicine concerned with the development of vaccines to control disease by identifying genetic and other mechanisms and pathways that determine immune responses, and thereby provide new candidate vaccine approaches.
D001428 Bacterial Vaccines Suspensions of attenuated or killed bacteria administered for the prevention or treatment of infectious bacterial disease. Bacterial Vaccine,Bacterin,Vaccine, Bacterial,Vaccines, Bacterial
D016680 Genome, Bacterial The genetic complement of a BACTERIA as represented in its DNA. Bacterial Genome,Bacterial Genomes,Genomes, Bacterial
D018984 Epitopes, T-Lymphocyte Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen. T-Cell Epitopes,T-Lymphocyte Epitopes,T-Cell Epitope,T-Lymphocyte Epitope,Epitope, T-Cell,Epitope, T-Lymphocyte,Epitopes, T Lymphocyte,Epitopes, T-Cell,T Cell Epitope,T Cell Epitopes,T Lymphocyte Epitope,T Lymphocyte Epitopes
D018985 Epitopes, B-Lymphocyte Antigenic determinants recognized and bound by the B-cell receptor. Epitopes recognized by the B-cell receptor are located on the surface of the antigen. B-Cell Epitopes,B-Lymphocyte Epitopes,B-Cell Epitope,B-Lymphocyte Epitope,B Cell Epitope,B Cell Epitopes,B Lymphocyte Epitope,B Lymphocyte Epitopes,Epitope, B-Cell,Epitope, B-Lymphocyte,Epitopes, B Lymphocyte,Epitopes, B-Cell
D022223 Vaccines, Subunit Vaccines consisting of one or more antigens that stimulate a strong immune response. They are purified from microorganisms or produced by recombinant DNA techniques, or they can be chemically synthesized peptides. Subunit Vaccine,Subunit Vaccines,Vaccine, Subunit

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