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A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
Outer Membrane Vesicle-Coated Nanoparticle Vaccine Protects Against Acinetobacter baumannii Pneumonia and Sepsis
Elisabet Bjanes1, Jiarong Zhou2, Tariq Qayum1
1Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, California 92093, USA.
Abstract:
The highly multidrug-resistant (MDR) Gram-negative bacterial pathogen Acinetobacter baumannii 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 A. baumannii 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 A. baumannii 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 A. baumannii and perhaps other high-priority MDR pathogens.
Insights
This study developed a novel nanoparticle-based vaccine using Acinetobacter baumannii outer membrane vesicles (Ab-OMVs). The Ab-NP vaccine effectively protected mice against lethal bacterial sepsis and pneumonia, offering a promising new strategy against multidrug-resistant pathogens.
Area of Science:
- Microbiology
- Immunology
- Nanotechnology
Background:
- Acinetobacter baumannii is a highly multidrug-resistant (MDR) Gram-negative pathogen and a global health priority.
- Outer membrane vesicles (OMVs) are potential vaccine candidates but are often heterogeneous.
- An effective vaccine could protect vulnerable populations and curb antimicrobial resistance.
Purpose of the Study:
- To develop and evaluate a novel vaccine platform combining nanoparticle technology with Acinetobacter baumannii outer membrane vesicles (Ab-OMVs).
- To assess the immunogenicity and protective efficacy of the Ab-OMV-coated nanoparticle vaccine (Ab-NPs) against A. baumannii infection.
Main Methods:
- Gold nanoparticle cores were coated with immunogenic Ab-OMVs to create Ab-NPs.
- Immunogenicity was assessed by measuring IgG titers in rabbits.
- Vaccine efficacy was evaluated in mouse models of sepsis and pneumonia, analyzing immune responses including B cell recruitment, dendritic cell activation, and cytokine levels.
Main Results:
- Ab-NP vaccination in rabbits induced robust IgG titers that enhanced human neutrophil opsonophagocytic killing.
- Passive immunization with Ab-NPs protected mice against lethal A. baumannii sepsis.
- Active immunization with Ab-NPs protected mice against sepsis and pneumonia, reducing proinflammatory cytokine storm and enhancing immune cell responses.
Conclusions:
- Nanoparticles serve as an efficient and effective platform for delivering OMV vaccines.
- The Ab-NP vaccine platform shows significant promise for combating Acinetobacter baumannii infections.
- This platform may be applicable to other high-priority multidrug-resistant pathogens.
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