STING-adjuvanted outer membrane vesicle nanoparticle vaccine against <i>Pseudomonas aeruginosa</i>

Elisabet Bjånes; Nishta Krishnan; Truman Koh; Anh T.P. Ngo; Jason Cole; Joshua Olson; Ingrid Cornax; Chih-Ho Chen; Natalie Chavarria; Samira Dahesh; Shawn M. Hannah; Alexandra Stream; Jiaqi Amber Zhang; Hervé Besançon; Daniel Sun; Siri Yendluri; Sydney Morrill; Jiarong Zhou; Animesh Mohapatra; Ronnie H. Fang; Victor Nizet

doi:10.1172/jci.insight.188105

¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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¹Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, United States of America

²Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, United States of America

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JCI Insight. https://doi.org/10.1172/jci.insight.188105.
Copyright © 2025, Bjånes et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published July 24, 2025 - Version history

Multidrug-resistant (MDR) bacterial pneumonias pose a critical threat to global public health. The opportunistic Gram-negative pathogen Pseudomonas aeruginosa is a leading cause of nosocomial-associated pneumonia, and an effective vaccine could protect vulnerable populations, including the elderly, immunocompromised, and those with chronic respiratory diseases. Highly heterogeneous outer membrane vesicles (OMVs), shed from Gram-negative bacteria, are studded with immunogenic lipids, proteins, and virulence factors. To overcome limitations in OMV stability and consistency, we described a believed to be novel vaccine platform that combines immunogenic OMVs with precision nanotechnology—creating a bacterial cellular nanoparticle vaccine candidate (CNP), termed Pa-STING-CNP, which incorporates an adjuvanted core that activates the STING (stimulator of interferon genes) pathway. In this design, OMVs are coated onto the surface of self-adjuvanted STING nanocores. Pa-STING CNP vaccination induced substantial antigen presenting cell recruitment and activation in draining lymph nodes, robust anti-Pseudomonas antibody responses, and provided protection against lethal challenge with the hypervirulent clinical P. aeruginosa isolate PA14. Antibody responses mediated this protection and provided passive immunity against the heterologous P. aeruginosa strain PA01. These findings provided evidence that nanotechnology can be used to create a highly efficacious vaccine platform against high priority MDR pathogens such as P. aeruginosa.

Version 1 (July 24, 2025): In-Press Preview

STING-adjuvanted outer membrane vesicle nanoparticle vaccine against Pseudomonas aeruginosa

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