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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.

Recent works of Soviet and foreign investigators confirm the important role of products of the vital activity of streptococcus in the development of the infectious process and immunity. Experimental studies on the influence of streptococcus allergen and streptolysin O, and on the combined effect of these two preparations on the immune antitetanus reorganization of the body were conducted. Tetanus intoxication in test animals proceeded more severely and basically terminated in a lethal outcome. Thus out of 11 guinea pigs which received streptococcus allergen and were immunized with tetanus toxoid, eight died with the presence of the typical symptoms of tetanus intoxication, and three were found in a state of tetanus intoxication degree I. Of the 13 pigs which received streptolysin O nine died, the remainder were found in a state of tetanus intoxication of degrees I, II, and III. Of the nine animals which received streptococcus allergen and streptolysin O, eight died and one pig was found in a state of tetanus intoxication degree I. Thus the inhibiting influence of streptococcus allergen and streptolysin O on the formation of immunity to the toxin of tetanus is confirmed by the more severe clinical course of tetanus intoxication and the greater mortality among test animals in comparison with control., Edited trans. of Voprosy Immunologii; Mezhvedomstvennyi Respublikanskii Sbornik (USSR) v4 p35-38 1969, by Charles T. Ostertag, Jr.