Mineralized Bacteria as a Potent Vaccine Against Staphylococcus aureus Infections

Abstract 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.