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A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
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STING-adjuvanted outer membrane vesicle nanoparticle vaccine against Pseudomonas aeruginosa

Elisabet Bjånes1, Nishta Krishnan2, Truman Koh1

  • 1Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics.

JCI Insight
|July 24, 2025
PubMed

Insights

A novel nanotechnology vaccine platform combines bacterial outer membrane vesicles with STING-activating nanocores. This cellular nanoparticle vaccine candidate (CNP) successfully protected against Pseudomonas aeruginosa pneumonia in preclinical models.

Area of Science:

  • Immunology
  • Nanotechnology
  • Microbiology

Background:

  • Multidrug-resistant bacterial pneumonias, particularly from Pseudomonas aeruginosa, are a significant global health concern.
  • Outer membrane vesicles (OMVs) from Gram-negative bacteria are immunogenic but face stability challenges for vaccine development.
  • There is a critical need for effective vaccines against high-priority multidrug-resistant pathogens.

Purpose of the Study:

  • To develop a novel vaccine platform for Pseudomonas aeruginosa using nanotechnology.
  • To create a bacterial cellular nanoparticle vaccine candidate (CNP) by combining OMVs with an adjuvant-loaded core.
  • To evaluate the immunogenicity and protective efficacy of the Pa-STING-CNP vaccine.

Main Methods:

  • Developed a novel vaccine platform by coating immunogenic outer membrane vesicles (OMVs) onto self-adjuvanted STING (stimulator of interferon genes) nanocores, creating Pa-STING-CNP.
  • Administered the Pa-STING-CNP vaccine candidate to preclinical models.
  • Assessed antigen-presenting cell recruitment and activation, antibody responses, and protection against lethal challenge with Pseudomonas aeruginosa.

Main Results:

  • Pa-STING-CNP vaccination induced significant antigen-presenting cell recruitment and activation in draining lymph nodes.
  • Robust anti-Pseudomonas antibody responses were observed following vaccination.
  • The vaccine provided significant protection against lethal challenge with a hypervirulent P. aeruginosa strain (PA14), with antibodies conferring passive immunity against a heterologous strain (PA01).

Conclusions:

  • Nanotechnology can be leveraged to create a stable and effective vaccine platform against challenging multidrug-resistant pathogens like Pseudomonas aeruginosa.
  • The Pa-STING-CNP vaccine candidate demonstrates potential as a highly efficacious solution for preventing P. aeruginosa-associated pneumonia.
  • This approach highlights the promise of combining bacterial components with advanced nanotechnology for next-generation vaccines.
Keywords:
Bacterial infectionsBacterial vaccinesInfectious diseaseMicrobiologyNanotechnologyVaccines

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