In Silico Design and Immunogenicity Studies of Two Multi-Epitope Vaccines against Klebsiella pneumoniae.
5 affiliations
- 1Intrahospital Infections Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
- 2Doctoral Program in Biomedical Sciences and Public Health, IMIENS, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain.
- 3Microbiology of Intestinal Diseases, Biology Department, Universitat de Girona, Girona, Spain.
- 4Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
- 5Eck Institute for Global Health, Notre Dame, IN, USA.
Abstract
Klebsiella pneumoniae represents an important clinical problem worldwide, causing infections in healthy and immunocompromised individuals that are often resistant to multiple antibiotics. The diversity of potential antigens encoded by K. pneumoniae makes the development of a protein-based vaccine that combines different antigens a promising strategy to achieve high vaccine coverage. This study employs 8 highly conserved virulence factors encoded by K. pneumoniae to construct multi-epitope vaccines. The target proteins used here are the fimbrial subunit MrkA, the outer membrane proteins and porins OmpA, OmpW, LamB, and PhoE, and the siderophore receptors FepA, FhuA, and Fiu. Two different immunoinformatics strategies (BEPI and VAXI) were followed to select one B cell epitope per protein for vaccine construct design. Whereas the BEPI-strategy prioritizes the B cell epitope prediction score, the VAXI-strategy gives importance to B cell epitope antigenicity score. The validated multi-epitope sequences were fused to the immunostimulatory PADRE peptide. BEPI- and VAXI-vaccine proteins were predicted to be stable and easily expressed in Escherichia coli and Homo sapiens. Moreover, both met the safety thresholds of non-allergenicity, non-toxicity, and non-human homology. Specifically, the VAXI-vaccine protein scored higher for solubility and antigenicity and was predicted to induce improved humoral and cellular responses. The predicted secondary structures of both vaccines consisted of >70% random coils, >15% α-helices, and ~10% β-strands, and their predicted 3-dimensional models indicated that most regions were exposed. Finally, >99.9% of global population coverage was predicted for both multi-epitope vaccines. We thus present 2 multi-epitope vaccines against K. pneumoniae virulence factors with promising physicochemical profiles regarding production and potential safety for preclinical testing and eventual use in humans.
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BibTeX
@article{vicentepazos2026silico,
title = {{In Silico Design and Immunogenicity Studies of Two Multi-Epitope Vaccines against Klebsiella pneumoniae.}},
author = {Marta Vicente-Pazos and Mireia López-Siles and Michael J McConnell},
journal = {Computational and structural biotechnology journal},
year = {2026},
month = oct,
doi = {10.34133/csbj.0232},
url = {https://europepmc.org/article/MED/42953336},
note = {CC BY},
}
RIS
TY - JOUR
TI - In Silico Design and Immunogenicity Studies of Two Multi-Epitope Vaccines against Klebsiella pneumoniae.
AU - Marta Vicente-Pazos
AU - Mireia López-Siles
AU - Michael J McConnell
PY - 2026
DA - 2026/10/28
JO - Computational and structural biotechnology journal
DO - 10.34133/csbj.0232
UR - https://europepmc.org/article/MED/42953336
AB - Klebsiella pneumoniae represents an important clinical problem worldwide, causing infections in healthy and immunocompromised individuals that are often resistant to multiple antibiotics. The diversity of potential antigens encoded by K. pneumoniae makes the development of a protein-based vaccine that combines different antigens a promising strategy to achieve high vaccine coverage. This study employs 8 highly conserved virulence factors encoded by K. pneumoniae to construct multi-epitope vaccines. The target proteins used here are the fimbrial subunit MrkA, the outer membrane proteins and porins OmpA, OmpW, LamB, and PhoE, and the siderophore receptors FepA, FhuA, and Fiu. Two different immunoinformatics strategies (BEPI and VAXI) were followed to select one B cell epitope per protein for vaccine construct design. Whereas the BEPI-strategy prioritizes the B cell epitope prediction score, the VAXI-strategy gives importance to B cell epitope antigenicity score. The validated multi-epitope sequences were fused to the immunostimulatory PADRE peptide. BEPI- and VAXI-vaccine proteins were predicted to be stable and easily expressed in Escherichia coli and Homo sapiens. Moreover, both met the safety thresholds of non-allergenicity, non-toxicity, and non-human homology. Specifically, the VAXI-vaccine protein scored higher for solubility and antigenicity and was predicted to induce improved humoral and cellular responses. The predicted secondary structures of both vaccines consisted of >70% random coils, >15% α-helices, and ~10% β-strands, and their predicted 3-dimensional models indicated that most regions were exposed. Finally, >99.9% of global population coverage was predicted for both multi-epitope vaccines. We thus present 2 multi-epitope vaccines against K. pneumoniae virulence factors with promising physicochemical profiles regarding production and potential safety for preclinical testing and eventual use in humans.
SN - 2001-0370
ER -