Exploring the potentials of Acinetobacter baumanii carbapenemase genes in the design of multi-epitope subunit vaccine using immunoinformatics approach

Abstract

Acinetobacter baumanii is currently being listed by the WHO as one of the priority organisms implicated in antimicrobial resistance which has mostly been ascribed to plasmid- and chromosome-encoded carbapenemases such as the OXA genes. This protein is a membrane porin of A. baumanii and the action of specific antibodies against it would exert bactericidal or bacteriostatic effect in-vitro. Thus, this study used an immunoinformatic approach to design a multi-epitope based vaccine that is targeted against A. baumanii infections using Bla-Oxa carbapenemase gene protein sequences. Methods and materials: Designed subunit vaccine was evaluated for its antigenicity, immunogenicity, allergenicity and physicochemical parameters. Results: A total of 109 CTL epitopes (9-mer) were predicted using NetCTL 1.2 server, among them only 4 epitopes with highranked binding affinity score were chosen as final CTL epitopes. Similarly, the HTL epitopes were identified using IEDB MHC-II prediction module based on the higher binding affinity with MHC- II, the mouse alleles used for the prediction were H2-1Ad, H2-1Ed, and H2-1Ab. A maximum immune response TLR-4 agonist (APPHALS) was used as an adjuvant and CTL epitopes were combined together by EAAAK linker, intra-CTL and intra-HTL epitopes joint by AAY and GPGPG linker to make a final vaccine construct of 472 amino acid residues designed using 4 CTL and 7 HTL epitopes. Conclusion: Collectively, this research provides novel candidates for epitope-based peptide vaccine design against Acinetobacter baumanii.