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Starch microparticles as oral vaccine adjuvant: antigen-dependent uptake in mouse intestinal mucosa
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: Journal of drug targeting (Print), ISSN 1061-186X, Vol. 12, no 5, 289-296 p.Article in journal (Refereed) Published
Abstract [en]

An oral vaccine formulation comprised of starch microparticles with conjugated antigens is being developed. In this report we have examined the uptake of such microparticles by the intestinal mucosa and examined whether the conjugated antigen can influence the uptake. Two model antigens were used: recombinant cholera toxin B subunit (rCTB), which is known to bind to the ubiquitous GM1-receptor, and human serum albumin (HSA) which is not known to have any specific binding properties. The uptake was studied in mouse ligated intestinal loops into which the microparticles were injected. The intestinal loops were excised, fixed in ice-cold 95% ethanol. Entire specimens were mounted, exposed to fluorescence-labeled reagents staining the cytoskeleton, the particles and/or M cells and examined in a confocal laser-scanning microscope. A qualitative difference in the uptake of the rCTB- and HSA-conjugated microparticles was seen. The rCTB-conjugated microparticles were found both in villi and in the follicles of the Peyer's patches. HSA-conjugated microparticles could only be detected in the follicles of the Peyer's patches and not in villi. The rCTB conjugated to the microparticles did not lose its ability to bind the GM1-receptor, as shown with a GM1-ELISA, and the uptake of rCTB-conjugated microparticles in villi is most probably facilitated by the rCTB binding to the GM1-receptor. The qualitative difference in uptake could be of importance for the development of an immune response as the cytokine and chemokine microenvironment during antigen presentation will decide the differentiation of the immune response induced.

Place, publisher, year, edition, pages
2004. Vol. 12, no 5, 289-296 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-92409DOI: 10.1080/1061186042000223662PubMedID: 15512780OAI: oai:DiVA.org:uu-92409DiVA: diva2:165472
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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