Reverse Vaccinology and Immunoinformatic Assisted Designing of a Multi-Epitopes Based Vaccine Against Nosocomial Burkholderia cepacia

Abstract

Burkholderia cepacia is a Gram-negative nosocomial pathogen and is considered as a troublesome bacterium due to its resistance to many common antibiotics. There is no licensed vaccine available to prevent the pathogen infections, thus making the condition more alarming and warrant the search for novel therapeutic and prophylactic approaches. In order to identify protective antigens from pathogen proteome, substantial efforts are put forth to prioritized potential vaccine targets and antigens that can be easily evaluated experimentally. In this vaccine design investigation, it was found that B. cepacia completely sequenced proteomes available in NCBI genome database has a total of 28,966 core proteins. Out of total, 25,282 proteins were found redundant while 3,684 were non-redundant. Subcellular localization revealed that 18 proteins were extracellular, 31 were part of the outer membrane, 75 proteins were localized in the periplasm, and 23 were virulent proteins. Five proteins namely flagellar hook protein (FlgE), fimbria biogenesis outer membrane usher protein, Type IV pilus secretin (PilQ), cytochrome c4, flagellar hook basal body complex protein (FliE) were tested for positive for antigenic, non-toxic, and soluble epitopes during predication of B-cell derived T-cell epitopes. A vaccine peptide of 14 epitopes (joined together via GPGPG linkers) and cholera toxin B subunit (CTBS) adjuvant (joined to epitopes peptide via EAAAK linker) was constructed. Binding interaction of the modeled vaccine with MHC-I, MHC-II, and Toll-like receptor 4 (TLR-4) immune receptors was studied using molecular docking studies and further analyzed in molecular dynamics simulations that affirms strong intermolecular binding and stable dynamics. The maximum root mean square deviation (RMSD) score of complexes in the simulation time touches to 2 Å. Additionally, complexes binding free energies were determined that concluded robust interaction energies dominated by van der Waals. The total energy of each complex is < −190 kcal/mol. In summary, the designed vaccine showed promising protective immunity against B. cepacia and needs to be examined in experiments.

Designing a novel Scaffold-Based Multi-Epitope Vaccine to Combat Melioidosis Caused by Burkholderia pseudomallei: AnIn-silicoand Immunoinformatics approach

“…There are very few treatment options available since clinical data indicate that all B. pseudomallei species are resistant to a variety of antibiotic classes, and some isolates are even resistant to front-line medications like ceftazidime and trimethoprim-sulfamethoxazole (TMP-SMX) [37]. Hence, developing new therapeutics against B. pseudomallei infection has become an active area of research [38,39].…”

Vaccinomics-based next-generation multi-epitope chimeric vaccine models prediction against Leishmania tropica - a hierarchical subtractive proteomics and immunoinformatics approach

“…Vaccine construct-V1 showed the lowest binding energy with the human TLR4 receptor. The thermodynamic stability of the V1-TLR4 complex was verified by binding affinity, normal mode dynamics, and immune simulations analyses ( 83 – 86 ). Immunogenic responses of TLR4 have been reported previously to inhibit parasite load and reduce inflammation in CL ( 82 ).…”

Improving Protection to Prevent Bacterial Infections: Preliminary Applications of Reverse Vaccinology against the Main Cystic Fibrosis Pathogens

“…However, some investigations against Bcc are also emerging. For instance, Alsowayeh and colleagues used a reverse vaccinology and immunoinformatic approach to predict effective antigens for the design of a multi-epitope chimeric vaccine; an in silico model was predicted to have strong interactions with host immune receptors [ 48 ]. Although only in silico studies have been performed at present, they should nevertheless provide a solid foundation for the future development of new vaccine candidates against B. cepacia complex.…”