Mineralized Bacteria as a Potent Vaccine Against <i>Staphylococcus aureus</i> Infections

Staphylococcus aureus (S. aureus) as common Gram-positive pathogenic bacteria, causes local and systemic infections, including sepsis and bacteremia. In particular, the high prevalence of drug-resistant S. aureus further complicates the post-infection treatment. Highly effective S. aureus vaccines are urgently desired. Herein, a novel S. aureus vaccine (MnO₂@FS) is developed via biomineralizing manganese dioxide (MnO₂) on formaldehyde-fixed S. aureus (FS). In such vaccine, with FS to induce bacteria-specific immune responses, MnO₂ via releasing Mn²⁺ can activate the cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) pathway and innate immunity, which would be rather helpful to enhance immune responses against bacterial infections. It is found that bone marrow-derived dendritic cells (BMDCs) treated with MnO₂@FS show higher FS and manganese uptake, and enhanced cytokine secretions. In mice, after being immunized with MnO₂@FS, the level of S. aureus-specific antibody is significantly improved compared with FS and simple mixture of FS and MnO₂ (FS+MnO₂). Furthermore, MnO₂@FS immunized mice can clear infected bacteria faster and showing higher survival rate in lethal models, outperforming FS and FS+MnO₂ immunizations. In addition, the vaccine effectively controls abscess development in a hospital-acquired S. aureus infection model. This study thus presents a new strategy for the construction of highly potent yet safe bacterial vaccines.