Biomimetic Neutrophil Nanotoxoids Elicit Potent Immunity against Acinetobacter baumanniiin Multiple Models of Infection

Acinetobacter baumanniiis a leading cause of antibiotic-resistant nosocomial infections with high mortality rates, yet there is currently no clinically approved vaccine formulation. During the onset of A. baumanniiinfection, neutrophils are the primary responders and play a major role in resisting the pathogen. Here, we design a biomimetic nanotoxoid for antivirulence vaccination by using neutrophil membrane-coated nanoparticles to safely capture secreted A. baumanniifactors. Vaccination with the nanotoxoid formulation rapidly mobilizes innate immune cells and promotes pathogen-specific adaptive immunity. In murine models of pneumonia, septicemia, and superficial wound infection, immunization with the nanovaccine offers significant protection, improving survival and reducing signs of acute inflammation. Lower bacterial burdens are observed in vaccinated animals regardless of the infection route. Altogether, neutrophil nanotoxoids represent an effective platform for eliciting multivalent immunity to protect against multidrug-resistant A. baumanniiin a wide range of disease conditions.