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Published on: February 27, 2019
Nanoparticle-based vaccine for mucosal protection against Shigella flexneri in mice
A I Camacho1, J M Irache, J de Souza
1Department of Microbiology, University of Navarra, 31008 Pamplona, Spain.
Abstract:
Shigellosis is one of the leading causes of diarrhea worldwide with more than 130 million cases annually. Hence, the research of an effective vaccine is still a priority. Unfortunately, a safe and efficacious vaccine is not available yet. We have previously demonstrated the capacity of outer membrane vesicles (OMVs) to protect mice against an experimental infection with Shigella flexneri. Now, we present results on the capacity of this antigenic complex to confer a longer-term protection by oral or nasal routes when encapsulated into nanoparticles. OMVs were encapsulated in poly(anhydride) nanoparticles (NP) prepared by a solvent displacement method with the copolymer poly methyl vinyl ether/maleic anhydride. OMVs loaded into nanoparticles (NP-OMVs) were homogeneous and spherical in shape, with a size of 148nm (PdI=0.2). BALB/c mice were immunized with OMVs either free or encapsulated in nanoparticles by nasal (20μg or 10μg of OMVs) or oral route (100μg or 50μg of OMVs). All immunized animals remained in good health after administration. Challenge infection was performed intranasally on week 8th with a lethal dose of 5×10(7)CFU/mouse of S. flexneri 2a. The number of dead mice after challenge was recorded daily. Results confirmed the value of OMVs as a vaccine. By oral route, the OMV-vaccine was able to protect independently either the dose or the formulation. When vaccine was delivered by nasal route, encapsulation into NPs resulted beneficial in increasing protection from 40% up to 100% when low dose was administered. These results are extraordinary promising and put in relevance the positive effect of nanoencapsulation of the OMV subcellular vaccine.
Insights
Outer membrane vesicles (OMVs) encapsulated in nanoparticles offer promising long-term protection against Shigellosis. Nanoencapsulation significantly enhances vaccine efficacy, particularly via nasal administration, providing a potential breakthrough for Shigella vaccines.
Area of Science:
- Vaccinology
- Nanotechnology
- Microbiology
Background:
- Shigellosis is a major global cause of diarrheal disease, necessitating effective vaccines.
- Current Shigella vaccines are limited, driving research into novel delivery systems.
- Outer membrane vesicles (OMVs) have shown potential as Shigella vaccine candidates.
Purpose of the Study:
- To evaluate the long-term protective capacity of OMVs against Shigella flexneri when delivered via oral or nasal routes using nanoparticles.
- To investigate the impact of nanoencapsulation on OMV vaccine efficacy and stability.
Main Methods:
- Outer membrane vesicles (OMVs) were encapsulated into poly(anhydride) nanoparticles (NP-OMVs).
- BALB/c mice were immunized with free OMVs or NP-OMVs via nasal or oral routes.
- Immunized mice were challenged with a lethal dose of Shigella flexneri 2a to assess protection.
Main Results:
- Both oral and nasal OMV-based vaccines demonstrated protective effects.
- Nanoencapsulation of OMVs significantly boosted protection, especially at lower doses via the nasal route, increasing efficacy from 40% to 100%.
- Oral administration provided protection irrespective of OMV dose or formulation.
Conclusions:
- Nanoencapsulation of OMVs is a promising strategy to enhance the efficacy and duration of Shigella vaccines.
- The NP-OMV formulation shows potential for developing a more effective Shigella vaccine, particularly for nasal delivery.
- Further research into nanoencapsulated OMVs could lead to improved Shigella prevention strategies.
