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

Abstract

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 towards the prevention of difficult-to-treat gram-negative infections.

Inhibition of Pathogen Adhesion by Bacterial Outer Membrane‐Coated Nanoparticles

“…Following the synthesis, the measurement of OM‐NPs with dynamic light scattering showed a hydrodynamic diameter of 105.7±3.1 nm (Figure B). The diameter increased by approximately 18 nm compared to that of the bare PLGA cores, consistent with the addition of a thin lipid bilayer onto the nanoparticle surface . Meanwhile, the surface zeta potential of the nanoparticles changed from −40.6±5.3 mV of PLGA cores to −28.8±1.9 mV of OM‐NPs.…”

CD4 + T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy

“…As therapeutic nanoparticles are gaining traction for potential HIV treatment and prevention, cell membrane-coated nanoparticles, made by wrapping plasma membranes of natural cells onto synthetic nanoparticle cores, are emerging as a biomimetic platform to treat various diseases ( 25 – 32 ). This unique biomimicry led us to assess this technology as a potential HIV treatment.…”

Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials

“…Recently, Wei et al [44] reported a macrophage-membrane-coated nanotoxoid against pathogenic Pseudomonas aeruginosa . It has already been reported previously that alveolar macrophages have cationic proteins that can bind to the outer membrane of the bacteria Pseudomonas aeruginosa, and its flagella also get involved in phagocytosis.…”

“…Hu et al [42] reported the first membrane-coated NPs where red blood cell (RBC) membranes were coated over a polymeric NP through extrusion [42]. Many types of membranes from different sources, such as RBCs [41,42,43], leukocytes [44,45,46], cytotoxic T-cells [47], NK cells [48], platelets [49], macrophages [44,50], and cancer cells [51,52], have been used in the preparation of membrane-coated NPs. Another type of biomimetic nanovaccine can be self-assembling proteins, which are known to have high symmetry and stability, and can be structurally organized into particles of sizes (10–150) nm [53,54].…”