Towards a Chimeric Vaccine against Multiple Isolates ofMycobacteroides- An Integrative Approach

Abstract

AbstractNontuberculous mycobacterial infection (NTM) such as endophthalmitis, dacryocystitis, canaliculitis are pervasive across the globe and are currently managed by antibiotics such as cefoxitin/imipenem and azithromycin/clarithromycin. However, the recent cases of Mycobacteroides developing drug resistance reported along with the improper practice of medicine intrigued us to explore its genomic and proteomic canvas at a global scale. A timely developed vaccine against Mycobacteroides is, therefore, a much requirement. Consequently, we carried out a vivid Genomic study on five recently sequenced strains of Mycobacteroides and explored their Pan-Core genome/ proteome. The promiscuous antigenic proteins were identified via a subtractive proteomics approach that qualified for virulence causation, resistance and essentiality factors for this notorious bacterium. An integrated pipeline was developed for the identification of B Cell, MHC class I, II epitopes. Our final vaccine construct, V6 qualified for all tests such as absence for allergenicity, presence of antigenicity, etc. and contains β defensin adjuvant, linkers, LAMP1 signal peptide, and PADRE (Pan HLA-DR epitopes) amino acid sequence. The vaccine construct, V6 also interacts with a maximum number of MHC molecules, and the TLR4/MD2 complex confirmed by docking and molecular dynamics simulation studies. The knowledge harnessed from the current study can help improve the current treatment regimens and propel further related studies.