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Starch microparticles as an adjuvnat in immunisation: effect of route of administration on the immune response in mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
2004 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 22, no 21-22, 2863-2872 p.Article in journal (Refereed) Published
Abstract [en]

This paper describes the effects on the development of an immune response by changing the route of administration of a new vaccine adjuvant, starch microparticles with human serum albumin (HSA) as a model antigen. The model vaccine was administered to mice by oral, subcutaneous and intramuscular routes in various combinations and both the local secretory immunoglobulin antibody (s-IgA) and systemic humoral and cellular (delayed-type hypersensitivity assay (DTH)) responses were followed. The only immunisation regimens inducing a significant s-IgA response were those incorporating oral booster doses. Oral and subcutaneous immunisations had similar effects on the Th1/Th2 balance, as indicated by the IgG subclass ratios and cytokine analyses. However, significant differences between oral and intramuscular immunisations were seen in the IgG subclass ratios. The Th2 influence was stronger after oral primary immunisation than after intramuscular primary immunisation, while oral boosters elicited a comparatively stronger Th1 response than intramuscular boosters. This result was also supported by the DTH analyses. Subcutaneous immunisation induced a stronger Th2 response than intramuscular immunisation, as indicated by subclass ratio and the IgE response. In conclusion, our results show that the profile of an immune response depends on the route of administration, which should be considered when developing new vaccines or new routes of administration.

Place, publisher, year, edition, pages
2004. Vol. 22, no 21-22, 2863-2872 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-92408DOI: 10.1016/j.vaccine.2003.12.019PubMedID: 15246622OAI: oai:DiVA.org:uu-92408DiVA: diva2:165471
Available from: 2004-11-25 Created: 2004-11-25 Last updated: 2013-05-29Bibliographically approved
In thesis
1. Starch Microparticles as an Oral Vaccine Adjuvant with Emphasis on the Differentiation of the Immune Response
Open this publication in new window or tab >>Starch Microparticles as an Oral Vaccine Adjuvant with Emphasis on the Differentiation of the Immune Response
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Polyacryl starch microparticles have been developed as an oral vaccine adjuvant capable of inducing strong local and systemic immune responses in mice. In this thesis, the starch microparticles were studied in order to increase basic understanding of their function. In particular, the thesis addressed aspects of the uptake of the particles and their presentation to the immune system after different routes of administration, in correlation with the differentiation of the induced immune response.

When using human serum albumin as a model antigen conjugated to the microparticles, it was found that the route of administration and the use of different combinations of routes, parenteral or oral, affect the profile (Th1/Th2 balance) of the induced immune response. It was also found that oral boosters are needed for the development of a local s-IgA response.

Ligated mouse intestinal loops in combination with confocal laser-scanning microscopy demonstrated that the uptake of the particles by the intestinal mucosa takes place over the follicle-associated epithelium (FAE) that covers the Peyer’s patches. The particles are also taken up in the villus epithelium when conjugated with rCTB, a ligand to the GM1 receptor. This qualitative difference in uptake did not affect the induced immune response. Thus, the addition of rCTB to the microparticles did not improve or influence the profile of the immune response. Chronic stress, known to alter the barrier function of the FAE, increased the cellular response but did not affect the humoral immune response.

Despite positive results in rodents, the particles were not able to boost a humoral immune response in man when tested with diphtheria toxin-cross reacting material (CRM197). Possible methods of improving the adjuvant effect in man are discussed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 56 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 317
Keyword
Pharmaceutics, Vaccine adjuvant, Microparticles, Oral immunisation, Th1/Th2 differentiation, Mucosal immune response, Uptake, M cell, Galenisk farmaci
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-4680 (URN)91-554-6101-8 (ISBN)
Public defence
2004-12-17, B42, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-11-25 Created: 2004-11-25Bibliographically approved

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