Toxin‐Responsive Antigen Reservoir Nanovaccines for In Situ Vaccination Against Bacterial Infection Recurrence

Abstract Current bacterial vaccines remain unsatisfactory in combating the increasing recurrence rates of drug‐resistant bacterial infections due to the inefficient activation of antigen presenting cells and the absence of long‐term immune memory. Here, a therapeutic nanovaccine (RBCM@PPPB) is engineered based on a photoimmunotherapy strategy and fabricated using polydopamine (PDA)‐modified Prussian blue nanoparticles, coated with targeting peptides and red blood cell membrane. These features enhance their biosafety and responsiveness to toxins from methicillin‐resistant Staphylococcus aureus (MRSA). The targeting peptides guide the nanoparticles to infection sites, allowing them to accumulate on the MRSA surface. Under near‐infrared irradiation, the photothermal bactericidal effect triggers the antigens release from dead MRSA, creating a diverse bacterial antigen library. PDA coating endows the nanoparticles with robust bacterial antigen‐gathering capacity, enabling in situ vaccination that enhances the antigen presentation process and subsequent MRSA‐specific adaptive immunity. Re‐challenge experiments demonstrated that RBCM@PPPB induced both cellular and humoral immune memory, significantly reducing recurrence risks. This study offers a proof‐of‐concept for “antigen reservoir” nanovaccines‐enhanced in situ vaccination, which establishes long‐term immune memory to prevent infection recurrence.