Vaccinomics to Design a Multi-Epitopes Vaccine for Acinetobacter baumannii

Abstract

Antibiotic resistance (AR) is the result of microbes’ natural evolution to withstand the action of antibiotics used against them. AR is rising to a high level across the globe, and novel resistant strains are emerging and spreading very fast. Acinetobacter baumannii is a multidrug resistant Gram-negative bacteria, responsible for causing severe nosocomial infections that are treated with several broad spectrum antibiotics: carbapenems, β-lactam, aminoglycosides, tetracycline, gentamicin, impanel, piperacillin, and amikacin. The A. baumannii genome is superplastic to acquire new resistant mechanisms and, as there is no vaccine in the development process for this pathogen, the situation is more worrisome. This study was conducted to identify protective antigens from the core genome of the pathogen. Genomic data of fully sequenced strains of A. baumannii were retrieved from the national center for biotechnological information (NCBI) database and subjected to various genomics, immunoinformatics, proteomics, and biophysical analyses to identify potential vaccine antigens against A. baumannii. By doing so, four outer membrane proteins were prioritized: TonB-dependent siderphore receptor, OmpA family protein, type IV pilus biogenesis stability protein, and OprD family outer membrane porin. Immuoinformatics predicted B-cell and T-cell epitopes from all four proteins. The antigenic epitopes were linked to design a multi-epitopes vaccine construct using GPGPG linkers and adjuvant cholera toxin B subunit to boost the immune responses. A 3D model of the vaccine construct was built, loop refined, and considered for extensive error examination. Disulfide engineering was performed for the stability of the vaccine construct. Blind docking of the vaccine was conducted with host MHC-I, MHC-II, and toll-like receptors 4 (TLR-4) molecules. Molecular dynamic simulation was carried out to understand the vaccine-receptors dynamics and binding stability, as well as to evaluate the presentation of epitopes to the host immune system. Binding energies estimation was achieved to understand intermolecular interaction energies and validate docking and simulation studies. The results suggested that the designed vaccine construct has high potential to induce protective host immune responses and can be a good vaccine candidate for experimental in vivo and in vitro studies.

Immunoinformatics- and Bioinformatics-Assisted Computational Designing of a Novel Multiepitopes Vaccine Against Cancer-Causing Merkel Cell Polyomavirus

“…Traditional vaccine is time consuming and very expensive (Delany et al, 2013 ). In this regard, computational vaccine designing could offer an attractive alternative platform to propose a novel vaccine construct for experimentalists to test the theoretical vaccine in tackling the pathogen (Seib et al, 2009 ; Albekairi et al, 2022a , b ; Ud-din et al, 2022 ). The computational vaccine design work on genomic information and uses a set of filters based on experimental data to identify the most suitable antigenic epitopes for experimental testing (Adu-Bobie et al, 2003 ; Suleman et al, 2021 ; Alharbi et al, 2022a , b ).…”

An In-Silico Investigation to Design a Multi-Epitopes Vaccine against Multi-Drug Resistant Hafnia alvei

“…This genome based approach identifies novel epitopes not reported previously. For example, the epitopes identified from the meningococcus genome were not surfaced by experimental techniques and thus led to the successful development of a vaccine [ 6 ].…”

“…It will take time to develop a vaccine that is safe to use in order to lower the burden of antibiotic resistance [ 5 ]. Only good vaccine availability can prevent antibiotic resistance [ 6 , 7 ]. Resistance to vaccines develops extremely rarely because vaccines are given before infection, which means they are prophylactic.…”

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

“…Antibiotic resistant bacterial pathogen can be managed by developing safe vaccines ( Jansen and Anderson, 2018 ; ud-din et al, 2022 ). Compared to antibiotics, vaccine resistance and associated allergic reactions are less.…”