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Polyacryl starch microparticles as adjuvant in oral immunisation, inducing mucosal and systemic immune responses in
Lena Wikingsson1, Ingvar Sjöholm
1Department of Pharmacy, Medical Products Agency, Box 26, SE-751 03 Uppsala, Sweden.
Abstract:
A new vaccine adjuvant for oral administration has been examined in mice. Polyacryl starch microparticles (2-3 microm in diameter) are prepared from a water-in oil-emulsion with stabilising hydrocarbon chains. A model antigen, human serum albumin (HSA), which is not binding to the gut epithelium, was covalently coupled to the highly porous starch particles. Upon oral administration, the HSA-microparticles induced a good, diversified immune response without any signs of tolerance development. A strong cellular response can be detected as a delayed-type hypersensitivity reaction. The Th1/Th2 ratio increased with the number of doses and time during the immunisation procedure as indicated by the subclass distribution of the systemic, humoral response. Furthermore, the mucosal response was very strong in the groups that received HSA-microparticles, while the groups receiving soluble HSA did not have any detectable s-IgA in faeces. The specificity was confirmed in an ELISPOT assay. These findings indicate that starch microparticles can be an interesting candidate as an oral vaccine adjuvant. The possible causes of the strong immune responses and the possible role of the dendritic cells in the diversified immune response are discussed.
Insights
New starch microparticles show promise as oral vaccine adjuvants in mice. These microparticles effectively stimulate diverse immune responses, including cellular and mucosal immunity, without inducing tolerance.
Area of Science:
- Immunology
- Vaccinology
- Biomaterials
Background:
- Developing effective oral vaccine adjuvants is crucial for improving vaccine delivery and efficacy.
- Starch microparticles offer a potential platform for oral drug and vaccine delivery due to their biocompatibility and biodegradability.
Purpose of the Study:
- To evaluate polyacryl starch microparticles as a novel oral vaccine adjuvant.
- To assess the immunogenicity and immune response profile induced by antigen-coupled starch microparticles.
Main Methods:
- Preparation of polyacryl starch microparticles and covalent coupling of human serum albumin (HSA) as a model antigen.
- Oral administration of HSA-coupled microparticles to mice.
- Assessment of cellular immune response (delayed-type hypersensitivity), humoral response (antibody subclasses), mucosal immunity (fecal s-IgA), and antigen specificity (ELISPOT assay).
Main Results:
- HSA-coupled starch microparticles induced a strong and diversified immune response without tolerance.
- A significant cellular immune response (delayed-type hypersensitivity) was observed.
- Increased Th1/Th2 ratio and strong mucosal s-IgA response in feces were detected.
- Specific immune response confirmed by ELISPOT assay.
Conclusions:
- Polyacryl starch microparticles are a promising candidate for oral vaccine adjuvants.
- Starch microparticles can effectively stimulate both systemic and mucosal immunity.
- Further research into the mechanisms, including the role of dendritic cells, is warranted.