Outer Membrane Vesicle‐Coated Nanoparticle Vaccine Protects against Acinetobacter baumannii Pneumonia and Sepsis

Abstract

The highly multidrug‐resistant (MDR) Gram‐negative bacterial pathogen Acinetobacter baumannii is a top global health priority where an effective vaccine can protect susceptible populations and limit resistance acquisition. Outer membrane vesicles (OMVs) shed from Gram‐negative bacteria are enriched with virulence factors and membrane lipids but heterogeneous in size and cargo. Herein, a vaccine platform combining precise and replicable nanoparticle technology with immunogenic A. baumannii OMVs (Ab‐OMVs) is reported. Gold nanoparticle cores coated with Ab‐OMVs (Ab‐NPs) induce robust IgG titers in rabbits that enhance human neutrophil opsonophagocytic killing and passively protect against lethal A. baumannii sepsis in mice. Active Ab‐NP immunization in mice protects against sepsis and pneumonia, accompanied by B cell recruitment to draining lymph nodes, activation of dendritic cell markers, improved splenic neutrophil responses, and mitigation of proinflammatory cytokine storm. Nanoparticles are an efficient and efficacious platform for OMV vaccine delivery against A. baumannii and perhaps other high‐priority MDR pathogens.

Outer Membrane Vesicles Released from Garlic Exosome‐like Nanoparticles (GaELNs) Train Gut Bacteria that Reverses Type 2 Diabetes via the Gut‐Brain Axis

“…[16,[52][53][54][55] This diversity within EVs stems from variances in their biogenesis, leading to classifications into different populations, further subdivided into various subsets. [53][54][55] OMVs, being extracellular nanovesicles released by bacteria, exhibit heterogeneity in size (40-300 nm diameter), [11,[56][57][58][59][60] where the size dictates both the entry into host cells and the protein composition. [61][62][63] In our investigation, we noted that a fraction of orally administered A. muciniphila OMVs evades uptake during the journey from the gut to the brain, escaping uptake by other cell types and ultimately being taken up by microglial cells.…”