The TamA protein as a subunit vaccine improves immune protection against highly virulent Klebsiella pneumoniae infection in mice

 Highlights

  • •
    Identification of the TamA protein as a highly conserved antigen across diverse Klebsiella pneumoniae strains, making it an ideal target for a broad-spectrum subunit vaccine.
  • •
    Development and evaluation of a recombinant TamA protein vaccine that significantly enhances immune protection against a highly virulent Klebsiella pneumoniae infection in a murine model.
  • •
    Demonstration of TamA-induced specific antibodies that effectively inhibit bacterial adherence to epithelial cells, thereby reducing bacterial load and pathological damage in vaccinated mice.
  • •
    Significant survival benefit observed in TamA-vaccinated mice, with 80 % surviving over 10 days following a lethal dose challenge, compared to controls that survived less than 48 h.
  • •
    Reduction in tissue bacterial loads and cytokine levels, along with mitigation of pathological changes in TamA-immunized mice, supporting the potential of TamA as a candidate vaccine for preventing Klebsiella pneumoniae infections.

Abstract

Vaccination is a promising strategy for preventing Klebsiella pneumoniae infection, yet strain heterogeneity poses a limitation. The optimal antigen target for an anti-Klebsiella pneumoniae vaccine should be expressed by all or most strains. This study identified the TamA protein as highly conserved across Klebsiella pneumoniae strains, irrelevant of serotype. A recombinant TamA protein vaccine was developed and evaluated for protective efficacy against lethal challenge in a murine model. The recombinant TamA was cloned in Escherichia coli and used to immunize mice, resulting in significantly higher total serum IgG concentrations compared to adjuvant-only controls, indicating robust antibody induction. In vitro experiments showed that TamA-induced specific antibodies blocked bacterial adherence to epithelial cells. Following a lethal dose challenge, 80% of TamA-vaccinated mice survived over 10 days, compared to less than 48 h for controls. The TamA recombinant protein vaccine provided protection, with significantly reduced bacterial loads and pathological changes in vaccinated mice. This study suggests TamA as a promising candidate vaccine for preventing Klebsiella pneumoniae infections.

Read full article for free (open access):
https://www.sciencedirect.com/science/article/pii/S2666517426000052



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