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bioRxiv · 10.1101/2019.12.15.869081

Towards a Chimeric Vaccine against Multiple Isolates of Mycobacteroides - An Integrative Approach

Satyam, R.·Bhardwaj, T.·Jha, N. K.
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Abstract

Nontuberculous 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 {beta} 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.

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Satyam, R., Bhardwaj, T., Jha, N. K.. 2019-12-15. Towards a Chimeric Vaccine against Multiple Isolates of Mycobacteroides - An Integrative Approach. https://doi.org/10.1101/2019.12.15.869081

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