Co-immunization with DNA vaccines encoding yidR and IL-17 augments host immune response against Klebsiella pneumoniae infection in mouse model

ABSTRACT

Klebsiella pneumoniae is an important gram-negative bacterium that causes severe respiratory and healthcare-associated infections. Although antibiotic therapy is applied to treat severe infections caused by K. pneumoniae, drug-resistant isolates pose a huge challenge to clinical practices owing to adverse reactions and the mismanagement of antibiotics. Several studies have attempted to develop vaccines against K. pneumoniae, but there are no licensed vaccines available for the control of K. pneumoniae infection. In the current study, we constructed a novel DNA vaccine, pVAX1-YidR, which encodes a highly conserved virulence factor YidR and a recombinant expression plasmid pVAX1-IL-17 encoding Interleukin-17 (IL-17) as a molecular adjuvant. Adaptive immune responses were assessed in immunized mice to compare the immunogenicity of the different vaccine schemes. The results showed that the targeted antigen gene was expressed in HEK293T cells using an immunofluorescence assay. Mice immunized with pVAX1-YidR elicited a high level of antibodies, induced strong cellular immune responses, and protected mice from K. pneumoniae challenge. Notably, co-immunization with pVAX1-YidR and pVAX1-IL-17 significantly augmented host adaptive immune responses and provided better protection against K. pneumoniae infections in vaccinated mice. Our study demonstrates that combined DNA vaccines and molecular adjuvants is a promising strategy to develop efficacious antibacterial vaccines against K. pneumoniae infections.

KEYWORDS:

• Klebsiella pneumoniae
• DNA vaccine
• recombinant proteins
• antibacterial immunity
• IL-17

Acknowledgements

The authors would like to thank Xiting Yang of Chu’s lab for the helpful support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

TH supervised the project; TH and ZL designed the experiments; ZL and XZ performed the experiments; LMD, KLZ, and XRW provided resources; TH and ZL analyzed the data and wrote the manuscript; TH, KLZ, and YWC provided funding. All authors have read and agreed to the final manuscript.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2024.2345019

Additional information

Funding

This research was funded by the International Science and Technology Cooperation Base Project of SIIA [ISTC202101], Science and Technology Bureau Program of Chengdu Municipal Government [2016-XT00-00023-GX], Sichuan Science and Technology Program [2021JDJQ0042], and Open project of Anti-infective Agent Creation Engineering Research Centre of Sichuan Province [AAC2023010].