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Updated: Nov 15, 2025
A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
Rapid prototyping vaccine approach in mice against multi-drug resistant Gram-negative organisms from clinical
Michael Pritsch1,2,3,4, Najib Ben Khaled1,5, Gabriele Liegl1
1Department of Bacteriology, Max von Pettenkofer-Institute (LMU), Munich, Germany.
Abstract:
Hospital-acquired infections due to multi-drug resistant Gram-negative organisms (MDRGNO) pose a major threat to global health. A vaccine preventing colonization and consecutive infection with MDRGNO could be particularly valuable, as therapeutic options become increasingly limited. Outer membrane vesicles (OMV) of Escherichia coli strain CFT073 as well as three MDRGNO strains that had caused severe infections in humans were administered intranasally to mice, with and without cholera toxin as an adjuvant. The humoral immune responses were comparatively matched with the sera of patients, who had suffered an infection caused by the respective bacterium. Additionally, systemic and local toxicity was evaluated. Intranasal vaccination with OMV could elicit solid humoral immune responses (total IgM and IgG), specific for the respective MDRGNO in mice; decoration of vital bacterial membranes with antibodies was comparable to patients who had survived systemic infection with the respective bacterial isolate. After intranasal vaccination of mice with OMV no signs of local or systemic toxicity were observed. Intranasal vaccination with OMV may open up a rapid vaccine approach to prevent colonization and/or infection with pathogenic MDRGNOs, especially in an outbreak setting within a hospital. It may also be an option for patients who have to undergo elective interventions in centers with a high risk of infection for certain common MDRGNO. Future studies need to include challenge experiments as well as phase I trials in humans.
Insights
Intranasal vaccination using outer membrane vesicles (OMV) shows promise for preventing multi-drug resistant Gram-negative organism infections. This approach elicits strong immune responses without observed toxicity in mice.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Hospital-acquired infections caused by multi-drug resistant Gram-negative organisms (MDRGNO) present a significant global health challenge.
- Limited therapeutic options necessitate novel strategies like vaccines to combat MDRGNO infections.
Purpose of the Study:
- To evaluate the efficacy of intranasal outer membrane vesicles (OMV) vaccination against MDRGNO.
- To assess the immunogenicity and toxicity of OMV vaccination in a preclinical model.
Main Methods:
- Outer membrane vesicles (OMV) from E. coli and three MDRGNO strains were administered intranasally to mice, with and without cholera toxin adjuvant.
- Humoral immune responses (IgM, IgG) were measured and compared to patient sera.
- Systemic and local toxicity was evaluated.
Main Results:
- Intranasal OMV vaccination induced robust, specific humoral immune responses against MDRGNO in mice.
- Antibody decoration of bacterial membranes was comparable to that observed in patients who recovered from infection.
- No local or systemic toxicity was detected following intranasal OMV vaccination.
Conclusions:
- Intranasal OMV vaccination is a potential rapid approach to prevent colonization and infection by pathogenic MDRGNOs.
- This strategy could be valuable in hospital outbreak settings and for patients undergoing elective procedures in high-risk environments.
- Further research, including challenge studies and human trials, is warranted.
