Multiantigenic Nanotoxoids for Antivirulence Vaccination against Antibiotic-Resistant Gram-Negative Bacteria

Infections caused
by multidrug-resistant Gram-negative bacteria
have emerged as a major threat to public health worldwide. The high
mortality and prevalence, along with the slow pace of new antibiotic
discovery, highlight the necessity for new disease management paradigms.
Here, we report on the development of a multiantigenic nanotoxoid
vaccine based on macrophage membrane-coated nanoparticles for eliciting
potent immunity against pathogenic Pseudomonas aeruginosa. The design of this biomimetic nanovaccine leverages the specific
role of macrophages in clearing pathogens and their natural affinity
for various virulence factors secreted by the bacteria. It is demonstrated
that the macrophage nanotoxoid is able to display a wide range of P. aeruginosa antigens, and the safety of the formulation
is confirmed both in vitro and in vivo. When used to vaccinate mice via different administration
routes, the nanotoxoid is capable of eliciting strong humoral immune
responses that translate into enhanced protection against live bacterial
infection in a pneumonia model. Overall, the work presented here provides
new insights into the design of safe, multiantigenic antivirulence
vaccines using biomimetic nanotechnology and the application of these
nanovaccines toward the prevention of difficult-to-treat Gram-negative
infections.