Multicomponent Pathogen-Mimicking Nanoparticles Induce Intestinal Immune Responses against Paratuberculosis
Yiduo Liu1, Meizhen Long1, Yuanzhi Wang1
1National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, P. R. China.
ACS Biomaterials Science & Engineering
|April 24, 2024
Summary
This study introduces PLGA-based nanoparticles (PLPCa NPs) for delivering novel antigens and adjuvants to combat enteric pathogens. These nanoparticles effectively stimulate both gut and systemic immunity, reducing bacterial load and inflammation.
Area of Science:
- Vaccinology
- Nanotechnology
- Immunology
Background:
- Enteric pathogens pose a global health challenge, necessitating advanced mucosal vaccine strategies.
- Developing safe and effective intestinal adjuvants and antigen delivery systems is crucial for mucosal vaccine design.
Purpose of the Study:
- To design and evaluate poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (PLPCa NPs) for co-delivering all-trans retinoic acid (atRA), novel antigens, and CpG.
- To create pathogen-mimicking nanoparticles for enhanced mucosal and systemic immunity against enteric pathogens.
Main Methods:
- Encapsulation of insoluble all-trans retinoic acid (atRA) within PLGA and polydopamine nanocapsids.
- Adsorption of water-soluble antigens (HBf fusion protein) and TLR9 agonist (CpG) onto the nanoparticle surface.
- In vitro assessment of dendritic cell activation and in vivo evaluation of immune responses and efficacy in a mouse model.
Main Results:
- PLPCa NPs demonstrated in vitro promotion of dendritic cell activation and maturation.
- Intramuscular administration of PLPCa NPs induced a localized immune-rich microenvironment.
- Significant induction of gut IgA and systemic immune responses was observed.
- PLPCa NPs treatment led to reduced bacterial burden and inflammation in mice.
Conclusions:
- PLPCa NPs represent a novel and safe vaccine delivery platform for targeting gut pathogens.
- This platform effectively activates both systemic and intestinal immunity, offering a promising approach for diseases like paratuberculosis.
