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Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres
Abstract:
Induction of systemic and mucosal immune responses following oral administration of biodegradable poly(D,L-lactic acid) (PDLLA) microspheres containing a model antigen, ovalbunin (OVA) was studied using microspheres with different average diameters of 0.6, 1.0, 4.0, 7.0, 11.0, 15.0, 21.0, and 26.0 microns. They were prepared from double emulsion with the solvent evaporation method, followed by size fractionation on counterflow elutriation. OVA was released from the microspheres in vitro over 80 days, irrespective of their size. Production of the serum anti-OVA IgG antibody and secretory OVA-specific IgA antibody in the mice gut was assessed following the oral administration of PDLLA microspheres containing OVA. Microspheres with a diameter of 4.0 microns enhanced the serum antibody in contrast with that of free OVA, but were not effective in inducing the gut secretion of IgA antibody. On the other hand, OVA-containing microspheres with a diameter of 7.0 microns enhanced IgA secretion to a significant extent compared with free OVA, whereas those with 26.0 microns in diameter were ineffective. Body distribution study revealed that the amount of microspheres taken up into Peyer's patches (PP) increased with the increasing size up to 11.0 microns, thereafter decreased, and finally became zero when their diameters were 21.0 microns or larger. The microspheres taken up into PP were translocated to the spleen, but no microspheres were noticed in the spleen when the size was larger than 5 microns. After being taken up inot PP, microspheres < 5 microns in diameter seemed to be transported to the spleen, a systemic lymphoid tissue, where the released antigen stimulated a serum antibody response, but larger microspheres probably remained at PP without being translocated to the spleen over the course of their antigen release, leading to induction of IgA secretion. It was concluded that the body distribution pattern of microspheres following the PP uptake was a key factor to regulate the induction of systemic and mucosal immune responses.
Insights
Microsphere size critically influences immune responses. Smaller microspheres (<5 microns) promote systemic antibody production, while larger ones (7 microns) enhance mucosal immunity by remaining in Peyer
Area of Science:
- Immunology
- Biomaterials Science
- Drug Delivery
Background:
- Biodegradable poly(D,L-lactic acid) (PDLLA) microspheres are investigated for oral antigen delivery.
- Understanding microsphere size effects on immune responses is crucial for vaccine development.
Purpose of the Study:
- To investigate the impact of poly(D,L-lactic acid) (PDLLA) microsphere size on systemic and mucosal immune responses.
- To determine the optimal microsphere size for inducing specific antibody production (IgG and IgA).
Main Methods:
- Preparation of PDLLA microspheres containing ovalbumin (OVA) with varying diameters (0.6–26.0 microns) using double emulsion solvent evaporation.
- In vitro release studies to assess antigen release kinetics.
- Oral administration to mice, followed by assessment of serum anti-OVA IgG and gut secretory OVA-specific IgA antibody production.
- Body distribution studies to track microsphere uptake in Peyer's patches (PP) and translocation to the spleen.
Main Results:
- Microsphere size significantly affected immune response induction; 4.0-micron microspheres enhanced serum IgG, while 7.0-micron microspheres significantly boosted IgA secretion.
- Microsphere uptake into Peyer's patches increased with size up to 11.0 microns, with translocation to the spleen observed for sizes < 5 microns.
- Larger microspheres (>5 microns) likely remained in Peyer's patches, promoting mucosal IgA response, whereas smaller ones transported to the spleen stimulated systemic IgG response.
Conclusions:
- Microsphere size dictates immune response type: smaller particles (<5 microns) favor systemic immunity, and larger particles (around 7 microns) promote mucosal immunity.
- The biodistribution pattern of microspheres within the Peyer's patch-spleen axis is a critical determinant of induced systemic versus mucosal immune responses.
- Tailoring microsphere size is a viable strategy for controlling the induction of specific immune responses for oral vaccine applications.