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

• 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 hours. • 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. 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 E. 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 hours 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. The graphical abstract presents the entire research process, including vector construction, vaccine preparation, and the study on vaccine efficacy. The image materials are sourced from the BioGDP database(Jiang et al., 2025).