Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology
Klebsiella pneumoniae is a Gram-negative pathogen of clinical relevance, which can provoke serious urinary and blood infections and pneumonia. This bacterium is a major public health threat due to its resistance to several antibiotic classes. Using a reverse vaccinology approach, 7 potential antigen...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022003695 |
| _version_ | 1797978156902121472 |
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| author | Nicola Cuscino Ayesha Fatima Vincenzo Di Pilato Matteo Bulati Caterina Alfano Elisa Monaca Giuseppina Di Mento Daniele Di Carlo Francesca Cardinale Francesco Monaco Gian Maria Rossolini Asif M. Khan Pier Giulio Conaldi Bruno Douradinha |
| author_facet | Nicola Cuscino Ayesha Fatima Vincenzo Di Pilato Matteo Bulati Caterina Alfano Elisa Monaca Giuseppina Di Mento Daniele Di Carlo Francesca Cardinale Francesco Monaco Gian Maria Rossolini Asif M. Khan Pier Giulio Conaldi Bruno Douradinha |
| author_sort | Nicola Cuscino |
| collection | DOAJ |
| description | Klebsiella pneumoniae is a Gram-negative pathogen of clinical relevance, which can provoke serious urinary and blood infections and pneumonia. This bacterium is a major public health threat due to its resistance to several antibiotic classes. Using a reverse vaccinology approach, 7 potential antigens were identified, of which 4 were present in most of the sequences of Italian carbapenem-resistant K. pneumoniae clinical isolates. Bioinformatics tools demonstrated the antigenic potential of these bacterial proteins and allowed for the identification of T and B cell epitopes. This led to a rational design and in silico characterization of a multiepitope vaccine against carbapenem-resistant K. pneumoniae strains. As adjuvant, the mycobacterial heparin-binding hemagglutinin adhesin (HBHA), which is a Toll-like receptor 4 (TLR-4) agonist, was included, to increase the immunogenicity of the construct. The multiepitope vaccine candidate was analyzed by bioinformatics tools to assess its antigenicity, solubility, allergenicity, toxicity, physical and chemical parameters, and secondary and tertiary structures. Molecular docking binding energies to TLR-2 and TLR-4, two important innate immunity receptors involved in the immune response against K. pneumoniae infections, and molecular dynamics simulations of such complexes supported active interactions. A codon optimized multiepitope sequence cloning strategy is proposed, for production of recombinant vaccine in classical bacterial vectors. Finally, a 3 dose-immunization simulation with the multiepitope construct induced both cellular and humoral immune responses. These results suggest that this multiepitope construct has potential as a vaccination strategy against carbapenem-resistant K. pneumoniae and deserves further validation. |
| first_indexed | 2024-04-11T05:19:35Z |
| format | Article |
| id | doaj.art-7ba7f4e86ad14e7bab076f47bcd67e1a |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:19:35Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-7ba7f4e86ad14e7bab076f47bcd67e1a2022-12-24T04:54:01ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012044464463Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinologyNicola Cuscino0Ayesha Fatima1Vincenzo Di Pilato2Matteo Bulati3Caterina Alfano4Elisa Monaca5Giuseppina Di Mento6Daniele Di Carlo7Francesca Cardinale8Francesco Monaco9Gian Maria Rossolini10Asif M. Khan11Pier Giulio Conaldi12Bruno Douradinha13Dipartimento di Ricerca, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, ItalyBeykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul, TurkeySOD Microbiologia e Virologia, Azienda Ospedaliera Universitaria Careggi, Florence, ItalyDipartimento di Ricerca, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, ItalyUnità di Biologia Strutturale e Biofisica, Fondazione Ri.MED, Palermo, ItalyUnità di Biologia Strutturale e Biofisica, Fondazione Ri.MED, Palermo, ItalyDipartimento di Ricerca, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, ItalyDipartimento di Ricerca, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, ItalyDipartimento di Ricerca, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, ItalyDipartimento di Ricerca, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, ItalySOD Microbiologia e Virologia, Azienda Ospedaliera Universitaria Careggi, Florence, Italy; Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Florence, ItalyBeykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul, Turkey; Centre for Bioinformatics, School of Data Sciences, Perdana University, Damansara Heights, Kuala Lumpur, MalaysiaDipartimento di Ricerca, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, ItalyDipartimento di Ricerca, IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Palermo, Italy; Unità di Medicina Rigenerativa ed Immunologia, Fondazione Ri.MED, Palermo, Italy; Corresponding author at: Fondazione Ri.MED c/o IRCCS-ISMETT, Via Ernesto Tricomi 5, Palermo 90127, Italy.Klebsiella pneumoniae is a Gram-negative pathogen of clinical relevance, which can provoke serious urinary and blood infections and pneumonia. This bacterium is a major public health threat due to its resistance to several antibiotic classes. Using a reverse vaccinology approach, 7 potential antigens were identified, of which 4 were present in most of the sequences of Italian carbapenem-resistant K. pneumoniae clinical isolates. Bioinformatics tools demonstrated the antigenic potential of these bacterial proteins and allowed for the identification of T and B cell epitopes. This led to a rational design and in silico characterization of a multiepitope vaccine against carbapenem-resistant K. pneumoniae strains. As adjuvant, the mycobacterial heparin-binding hemagglutinin adhesin (HBHA), which is a Toll-like receptor 4 (TLR-4) agonist, was included, to increase the immunogenicity of the construct. The multiepitope vaccine candidate was analyzed by bioinformatics tools to assess its antigenicity, solubility, allergenicity, toxicity, physical and chemical parameters, and secondary and tertiary structures. Molecular docking binding energies to TLR-2 and TLR-4, two important innate immunity receptors involved in the immune response against K. pneumoniae infections, and molecular dynamics simulations of such complexes supported active interactions. A codon optimized multiepitope sequence cloning strategy is proposed, for production of recombinant vaccine in classical bacterial vectors. Finally, a 3 dose-immunization simulation with the multiepitope construct induced both cellular and humoral immune responses. These results suggest that this multiepitope construct has potential as a vaccination strategy against carbapenem-resistant K. pneumoniae and deserves further validation.http://www.sciencedirect.com/science/article/pii/S2001037022003695Klebsiella pneumoniaeReverse vaccinologyAntimicrobial resistanceCarbapenemsSubunit vaccineBioinformatics |
| spellingShingle | Nicola Cuscino Ayesha Fatima Vincenzo Di Pilato Matteo Bulati Caterina Alfano Elisa Monaca Giuseppina Di Mento Daniele Di Carlo Francesca Cardinale Francesco Monaco Gian Maria Rossolini Asif M. Khan Pier Giulio Conaldi Bruno Douradinha Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology Computational and Structural Biotechnology Journal Klebsiella pneumoniae Reverse vaccinology Antimicrobial resistance Carbapenems Subunit vaccine Bioinformatics |
| title | Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology |
| title_full | Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology |
| title_fullStr | Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology |
| title_full_unstemmed | Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology |
| title_short | Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology |
| title_sort | computational design and characterization of a multiepitope vaccine against carbapenemase producing klebsiella pneumoniae strains derived from antigens identified through reverse vaccinology |
| topic | Klebsiella pneumoniae Reverse vaccinology Antimicrobial resistance Carbapenems Subunit vaccine Bioinformatics |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022003695 |
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