Protection Against Pneumonia Induced by Vaccination with Fimbriae Subunits from Klebsiella pneumoniae
(2025) In Vaccines 13(3).- Abstract
Background: Klebsiella pneumoniae infections pose a great burden worldwide, causing high morbidity and mortality, which are worsened by the increase in multidrug-resistant strains. New therapeutic/prophylactic strategies are urgently needed to overcome antibiotic resistance and reduce the health and economic impacts of diseases caused by this pathogen. Fimbriae are important virulence factors involved in biofilm formation and adhesion to host cells. Their exposed location, conservation among clinical isolates and adjuvant properties make them interesting candidates for inclusion in protein-based vaccines. Therefore, the present work investigated the immunological potential of type 1 and 3 fimbriae subunits in a murine model of K.... (More)
Background: Klebsiella pneumoniae infections pose a great burden worldwide, causing high morbidity and mortality, which are worsened by the increase in multidrug-resistant strains. New therapeutic/prophylactic strategies are urgently needed to overcome antibiotic resistance and reduce the health and economic impacts of diseases caused by this pathogen. Fimbriae are important virulence factors involved in biofilm formation and adhesion to host cells. Their exposed location, conservation among clinical isolates and adjuvant properties make them interesting candidates for inclusion in protein-based vaccines. Therefore, the present work investigated the immunological potential of type 1 and 3 fimbriae subunits in a murine model of K. pneumoniae lung infection. Methods: MrkA and FimA were produced as recombinant proteins in E. coli, purified and used to immunize mice subcutaneously. The immune responses were characterized and protection against pneumonia was evaluated after intranasal challenge. Results: Subcutaneous immunization with recombinant FimA and MrkA induced high IgG1 production; the antibodies efficiently recognized the native proteins at the bacterial surface, promoted C3 deposition and reduced biofilm formation by K. pneumoniae in vitro. Mice vaccinated with the co-administered proteins reduced the bacterial loads in the lungs after intranasal challenge, less inflammation and reduced tissue damage. Conclusion: The results suggest that both type 1 and type 3 fimbriae contribute to protection against K. pneumoniae lung infection, inducing antibodies that bind to the bacteria and favoring Complement deposition and clearance by the host, while inhibiting biofilm formation.
(Less)
- author
- Assoni, Lucas
; Ciaparin, Isabelle
; Trentini, Monalisa Martins
; Baboghlian, Juliana
; Rodrigo, Gabriel
; Ferreira, Brenda Vieira
; Pereira, José Aires
; Martinez, Carlos
; Ferraz, Lucio
; Girardello, Raquel
; Carvalho, Lucas Miguel
; Hakansson, Anders P.
LU
; Converso, Thiago Rojas
LU
and Darrieux, Michelle
LU
(Less) - organization
- publishing date
- 2025-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- biofilms, fimbriae, K. pneumoniae, protein vaccines
- in
- Vaccines
- volume
- 13
- issue
- 3
- article number
- 303
- publisher
- MDPI AG
- external identifiers
-
- pmid:40266206
- scopus:105001121452
- ISSN
- 2076-393X
- DOI
- 10.3390/vaccines13030303
- language
- English
- LU publication?
- yes
- id
- 30728ba4-b5f6-402f-96a6-1d2d4a684ef1
- date added to LUP
- 2025-08-26 11:41:37
- date last changed
- 2025-09-09 12:41:50
@article{30728ba4-b5f6-402f-96a6-1d2d4a684ef1,
abstract = {{<p>Background: Klebsiella pneumoniae infections pose a great burden worldwide, causing high morbidity and mortality, which are worsened by the increase in multidrug-resistant strains. New therapeutic/prophylactic strategies are urgently needed to overcome antibiotic resistance and reduce the health and economic impacts of diseases caused by this pathogen. Fimbriae are important virulence factors involved in biofilm formation and adhesion to host cells. Their exposed location, conservation among clinical isolates and adjuvant properties make them interesting candidates for inclusion in protein-based vaccines. Therefore, the present work investigated the immunological potential of type 1 and 3 fimbriae subunits in a murine model of K. pneumoniae lung infection. Methods: MrkA and FimA were produced as recombinant proteins in E. coli, purified and used to immunize mice subcutaneously. The immune responses were characterized and protection against pneumonia was evaluated after intranasal challenge. Results: Subcutaneous immunization with recombinant FimA and MrkA induced high IgG1 production; the antibodies efficiently recognized the native proteins at the bacterial surface, promoted C3 deposition and reduced biofilm formation by K. pneumoniae in vitro. Mice vaccinated with the co-administered proteins reduced the bacterial loads in the lungs after intranasal challenge, less inflammation and reduced tissue damage. Conclusion: The results suggest that both type 1 and type 3 fimbriae contribute to protection against K. pneumoniae lung infection, inducing antibodies that bind to the bacteria and favoring Complement deposition and clearance by the host, while inhibiting biofilm formation.</p>}},
author = {{Assoni, Lucas and Ciaparin, Isabelle and Trentini, Monalisa Martins and Baboghlian, Juliana and Rodrigo, Gabriel and Ferreira, Brenda Vieira and Pereira, José Aires and Martinez, Carlos and Ferraz, Lucio and Girardello, Raquel and Carvalho, Lucas Miguel and Hakansson, Anders P. and Converso, Thiago Rojas and Darrieux, Michelle}},
issn = {{2076-393X}},
keywords = {{biofilms; fimbriae; K. pneumoniae; protein vaccines}},
language = {{eng}},
number = {{3}},
publisher = {{MDPI AG}},
series = {{Vaccines}},
title = {{Protection Against Pneumonia Induced by Vaccination with Fimbriae Subunits from Klebsiella pneumoniae}},
url = {{http://dx.doi.org/10.3390/vaccines13030303}},
doi = {{10.3390/vaccines13030303}},
volume = {{13}},
year = {{2025}},
}