Identification and construction of a multi-epitopes vaccine design against Klebsiella aerogenes: molecular modeling study

Abstract

A rapid rise in antibiotic resistance by bacterial pathogens is due to these pathogens adaptation to the changing environmental conditions. Antibiotic resistance infections can be reduced by a number of ways such as development of safe and effective vaccine. Klebsiella aerogene is a gram-negative, rod-shaped bacterium resistant to a variety of antibiotics and no commercial vaccine is available against the pathogen. Identifying antigens that can be easily evaluated experimentally would be crucial to successfully vaccine development. Reverse vaccinology (RV) was used to identify vaccine candidates based on complete pathogen proteomic information. The fully sequenced proteomes include 44,115 total proteins of which 43,316 are redundant and 799 are non-redundant. Subcellular localization showed that only 1 protein in extracellular matrix, 7 were found in outer-membrane proteins, and 27 in the periplasm space. A total of 3 proteins were found virulent. Next in the B-cell-derived T-cell epitopes mapping phase, the 3 proteins (Fe2+− enterobactin, ABC transporter substrate-binding protein, and fimbriae biogenesis outer membrane usher protein) were tested positive for antigenicity, toxicity, and solubility. GPGPG linkers were used to prepare a vaccine construct composed of 7 epitopes and an adjuvant of toxin B subunit (CTBS). Molecular docking of vaccine construct with major histocompatibility-I (MHC-I), major histocompatibility-II (MHC-II), and Toll-like receptor 4 (TLR4) revealed vaccine robust interactions and stable binding pose to the receptors. By using molecular dynamics simulations, the vaccine-receptors complexes unveiled stable dynamics and uniform root mean square deviation (rmsd). Further, binding energies of complex were computed that again depicted strong intermolecular bindings and formation of stable conformation.

Proteomics-based vaccine targets annotation and design of multi-epitope vaccine against antibiotic-resistant Streptococcus gallolyticus

“…Seven well-known pathogenic S. gallolyticus strains were considered for vaccine development, and their core proteome analysis was performed. Because core proteins are present in all or most strains of the pathogen being targeted and their presence in vaccine development offers immune protection against a broader range of pathogen species, they are now being studied in the creation of vaccines 69 . The core proteome underwent a subtractive proteomics procedure to reveal essential, non-homologous, antigenic, immunogenic, and allergenic proteins for a vaccine.…”

An immunoinformatics and structural vaccinology approach to design a novel and potent multi-epitope base vaccine targeting Zika virus

“…Vaccination is one of the important methods to prevent from infectious diseases [ 38 ], including reverse vaccinology, which is used to develop a multi-epitope vaccine, due to its efficiency and cost-effectiveness. Different protective, stable and safe vaccines were designed to prevent infectious diseases [ 39 ], including Burkholderia pseudomallei [ 40 ], SAR-CoV-2 [ 41 ], Lumpy skin disease [ 42 ], Monkey Pox [ 43 ], Helicobacter pylori [ 44 ], Aeromonas hydrophilla [ 45 ], and Klebsiella pneumonia [ 46 ]. Therefore, we our study focused to developed a potent multi-epitope based vaccine targeting Zika virus.…”

Design of a Multi-Epitope Vaccine against Tuberculosis from Mycobacterium tuberculosis PE_PGRS49 and PE_PGRS56 Proteins by Reverse Vaccinology

“…In the vaccine design, the selected epitopes were separated by the GPGPG linker, and EAAAK linkers were added at the N-terminus of the construct [ 31 , 41 , 51 ]. RS09 adjuvant was also included, which is a bacterial LPS mimic that activates TLR4 [ 36 ].…”