Outer Membrane Vesicle‐Coated Nanoparticle Vaccine Protects against <i>Acinetobacter baumannii</i> Pneumonia and Sepsis

Abstract

The highly multidrug-resistant (MDR) Gram-negative bacterial pathogen <i>Acinetobacter baumannii</i> is a top global health priority where an effective vaccine could 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. We report a vaccine platform combining precise and replicable nanoparticle technology with immunogenic <i>A. baumannii</i> OMVs (Ab-OMVs). Gold nanoparticle cores coated with Ab-OMVs (Ab-NPs) induced robust IgG titers in rabbits that enhanced human neutrophil opsonophagocytic killing and passively protected against lethal <i>A. baumannii</i> sepsis in mice. Active Ab-NP immunization in mice protected 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 <i>A. baumannii</i> and perhaps other high-priority MDR pathogens.