Publication: Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology
Loading...
Date
2022-01-01T00:00:00Z
Authors
Cuscino, Nicola
Fatima, Ayesha
Di Pilato, Vincenzo
Bulati, Matteo
Alfano, Caterina
Monaca, Elisa
Di Mento, Giuseppina
Di Carlo, Daniele
Cardinale, Francesca
Monaco, Francesco
Journal Title
Journal ISSN
Volume Title
Publisher
Metrics
Abstract
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.
Description
Keywords
Klebsiella pneumoniae, Reverse vaccinology, Antimicrobial resistance, Carbapenems, Subunit vaccine, Bioinformatics
Citation
Cuscino N., Fatima A., Di Pilato V., Bulati M., Alfano C., Monaca E., Di Mento G., Di Carlo D., Cardinale F., Monaco F., et al., -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, cilt.20, ss.4446-4463, 2022