Manganese‐Based Nanoparticle Vaccine for Combating Fatal Bacterial Pneumonia

Abstract Bacterial pneumonia is the leading cause of death worldwide among all infectious diseases. However, currently available vaccines against fatal bacterial lung infections, e.g., pneumonic plague, are accompanied by limitations, including insufficient antigen‐adjuvant co‐delivery and inadequate immune stimulation. Therefore, there is an urgent requirement to develop next‐generation vaccines to improve the interaction between antigen and adjuvant, as well as enhance the effects of immune stimulation. This study develops a novel amino‐decorated mesoporous manganese silicate nanoparticle (AMMSN) loaded with rF1‐V10 (rF1‐V10@AMMSN) to prevent pneumonic plague. These results suggest that subcutaneous immunization with rF1‐V10@AMMSN in a prime‐boost strategy induces robust production of rF1‐V10‐specific IgG antibodies with a geometric mean titer of 315,844 at day 42 post‐primary immunization, which confers complete protection to mice against 50 × LD₅₀ of Yersinia pestis (Y. pestis) challenge via the aerosolized intratracheal route. Mechanistically, rF1‐V10@AMMSN can be taken up by dendritic cells (DCs) and promote DCs maturation through activation of the cyclic GMP–AMP synthase (cGAS)‐stimulator of interferon genes (STING) pathway and production of type I interferon. This process results in enhanced antigen presentation and promotes rF1‐V10‐mediated protection against Y. pestis infection. This manganese‐based nanoparticle vaccine represents a valuable strategy for combating fatal bacterial pneumonia.