Background The lack of appropriate vaccines is an obstacle to the effective management of A. baumannii infections. Peptide vaccines offer an attractive and promising preventive strategy against A. baumannii. Objective In this study, we identified specific T cell epitopes of A. baumannii outer membrane protein K (OMPK) using comprehensive bioinformatics and detailed molecular docking analysis. Methods Both class-I and class-II T cell epitopes of A. baumannii OMPK were predicted by three tools namely IEDB, SYFPEITHI, and ProPred. The predicted epitopes were shortlisted based on several analyses including prediction scoring, clustering, exclusion of human similarity, considering immunogenicity and cytokine production, and removal of toxic and/or allergen epitopes. The epitopic peptides with high prediction scores and appropriate properties containing both class-I and class-II T cell epitopes were selected. Two of these class I/II epitopic peptides were chosen for molecular docking studies and assessing their physicochemical properties as vaccine candidates. Results The results showed many T-cell epitopes of OMPK that could be evaluated for possible immunogenicity. Two of these epitopes (containing both class-I and II epitopes) had high prediction scores, were predicted by several tools, attached to several HLAs, and had the best docking score. They had different physicochemical properties and were conserved among Acinetobacter species. Discussion We identified the A. baumannii OMPK high immunogenic class-I and class-II T cell epitopes and introduced two promising high immunogenic peptides as vaccine candidates. It is recommended to perform in vitro/in vivo investigation of these peptides to determine their true efficacy and efficiency.
No approved vaccine exists for Klebsiella pneumoniae yet. Outer membrane protein-K17 (OMPK17) is involved in K. pneumoniae pathogenesis. No information has been found about OMPK17 dominant epitopes in the literature. Therefore, this study aimed to predict both T cell and B cell epitopes of K. pneumoniae OMPK17 via immunoinformatics approaches. Both T cell (class-I and II) and B cell (linear and discontinuous) epitopes of OMPK17 were predicted. Several screening analyses were performed including clustering, immunogenicity, human similarity, toxicity, allergenicity, conservancy, docking, and structural/physicochemical suitability. The results showed that some regions of OMPK17 have more potential as epitopes. The most possible epitopes were found via several analyses including the selection of higher-scoring epitopes, the epitopes predicted with more tools, more immunogenic epitopes, the epitopes capable of producing interferon-gamma, the epitopes with more dissimilarity to human peptides, and non-toxic and non-allergenic epitopes. By comparing the best T cell and B cell epitopes, we reached a 25-mer peptide containing both T cell (class-I and class-II) and B cell (linear) epitopes and comprising appropriate physicochemical characteristics that are required for K. pneumoniae vaccine development. The in vitro/in vivo study of this peptide is recommended to clarify its actual efficiency and efficacy. Keywords Epitope • Immunoinformatics• Klebsiella pneumoniae • Outer membrane protein-K17 • Physicochemical characteristics Abbreviations CPORT Consensus prediction of interface residues in transient complexes GQE Global Quality Estimate GRAVY Grand average of hydropathicity index HLA Human leukocyte antigen IFN-γ Inte rferon-gamma LQE Local Quality Estimate OMP Outer membrane protein OMPK17 Outer membrane protein-K17 pI Isoelectric pH QMEAN Qualitative model energy analysis SDAP Structural database of allergenic proteins * Mosayeb Rostamian
Background The lack of appropriate vaccines is an obstacle to the effective management of A. baumannii infections. Peptide vaccines can provide attractive and promising preventive strategies against A. baumannii. Objective Here, specific T cell epitopes of A. baumannii outer membrane protein K (OMPK) were found using comprehensive bioinformatics and detailed molecular docking analysis. Methods Both class-I and class-II T cell epitopes of A. baumannii OMPK were predicted by three tools namely IEDB, SYFPEITHI, and ProPred. The predicted epitopes were shortlisted via several analyses such as prediction scoring, clustering, human similarity exclusion, considering immunogenicity and cytokine production, and removing toxic and/or allergen epitopes. The epitopic peptides with high prediction scores and appropriate properties that contained both class-I and class-II T cell epitopes were selected. Two of these class I/II epitopic peptides were chosen for molecular docking studies and assessing their physicochemical properties as vaccine candidates. Results The results showed many T-cell epitopes of OMPK that could be evaluated for possible immunogenicity. Two of these epitopes (containing both class-I and II epitopes) had high prediction scores, predicted by several tools, attached to several HLAs, and had the best docking score (bind efficiently to their specific HLAs). They had different physicochemical properties and were conserved among Acinetobacter species. Discussion We identified the A. baumannii OMPK high immunogenic class-I and class-II T cell epitopes and introduced two promising high immunogenic peptides as vaccine candidates. It is recommended to do an in vitro/in vivo investigation of these peptides to determine their true efficacy and efficiency.
Acinetobacter baumannii is a significant cause of hospital-acquired infections and is often resistant to multiple antibiotics. In this study, we designed a multi-epitope vaccine candidate using the outer membrane protein K (OmpK) of A. baumannii. T-cell and B-cell epitopes were predicted, and the best epitopes were selected for multi-epitope design. For selecting the best epitopes, many in silico studies, as well as molecular docking of epitope-HLAs, were performed. The multi-epitope was designed using β-defensin as an adjuvant, PADRE sequence as an immunogenicity enhancer, and appropriate linkers. The tertiary structure of the multi-epitope was obtained using modeling and several molecular dynamics (MD)-based refinements. The sequence and/or 3D model of the multi-epitope was investigated for physicochemical, structural, in silico cloning, conformational B epitope prediction, immune response simulation, molecular docking for assay binding to toll-like receptors (TLRs), and deformability studies. The results showed that the multi-epitope construct is favorable in the case of immunogenicity, physicochemical properties, structure, binding to TLRs, solubility, stability, toxicity, allergenicity, and cross-reactivity. This multi-epitope vaccine candidate has the potential to elicit multiple immune responses against A. baumannii. However, in vitro and in vivo experimental tests are needed to validate its efficacy as a potential vaccine candidate.
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