Peptide vaccine identification against Mycobacterium tuberculosis through combinatorial/integrated pan-genomics and reverse vaccinology approaches

Abstract

Mycobacterium tuberculosis has become an eminent healthcare concern for society because of its growing rates of morbidity and mortality in cases pulmonary and extra-pulmonary tuberculosis infections. The alarming situation of antibiotic resistance and lack of protective response of current vaccines requires cost–effective potent vaccine development. In the current study we have scrutinized the Mycobacterium tuberculosis genome utilizing integrated pangenomics and reverse vaccinology approaches. The pan-genome analysis of 47 completely sequenced strains avaiable at the time of analysis revealed 5,069 functional genes and 3,170 (62% of the pan-genome) were found to beconstituting the core-genome. The phylogenetic analysis intra and inter genome homology on the basis of geographical distribution. Among the conserved eight proteins found to have a potent antigenic potential namely, Esterase, Secreted antigen 85-C (85C), PPE family protein, ESX conserved component 5, lysine-N-oxygenase, ESX-2 secretion system 2, Exported repetitive partial and thiol peroxidase. All these vaccines fulfilled the essential criterias of vaccin candidates assortment including host non-homolohy, virulence, essentiality and conservation. The function annotation and protein-protein interaction analysis showed them to actively involve in significant biologica and molecular processes. These propitious vaccine candidates on epotope mapping generated antigenic 9-mer immunogenic T-cell epitopes. The study, established upon integrated strategy of pan-genomics and reverse vaccinology revealed potential vaccine candidates against Mycobacterium tuberculosis. The inclusive analysis of all the completely sequenced genomes discovered eight putative antigens which could initiate substantial protective immune response against all Mycobacterium tuberculosis strains . 2 The antigenic epitopes identified in the vaccine candidates can be utilized for the development of a cost effective mutivalent peptide or recombinant vaccine against Mycobacterium tuberculosis.