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Mucosal Vaccination Using Polyacryl Starch Microparticles as Adjuvant with Salmonella enteritidis as a Model Pathogen
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Polyacryl starch microparticles have been developed as a new mucosal vaccine adjuvant intended for use in oral vaccination. The main objectives of this thesis were to evaluate the efficacy of these polyacryl starch microparticles and to study their uptake through mucosal tissues. Secreted or surface components of Salmonella enterica serovar Enteritidis were used in free form or were conjugated to or mixed with the microparticles in vaccination studies in mice in order to find components suitable for use in a future combination vaccine against enteric bacteria such as enterotoxigenic Escherichia coli.

The immune response elicited using secreted proteins from S. enterica serovar Enteritidis was shown to be mainly directed against flagella-related antigens and partly by LPS. Flagellin was purified and used in C3H/HeJ mice that do not respond to LPS. Strong immune responses were observed even when the flagellin was given orally alone. Recombinant Salmonella atypical fimbriae (SafB/D) complexes, a conserved structure within Salmonella species, were also studied and shown to be immunogenic after administration both subcutaneously and nasally, but not orally. Oral challenge using live bacteria, showed that mice orally immunised with the secreted antigens, resulted in a lower degree of infection than that seen in non-vaccinated mice. Similarly, mice that had been immunised with purified free flagellin had a lower degree of infection than untreated mice. However, with mice, immunised with SafB/D complexes plus rCTB, only the subcutaneous route resulted in a lower degree of infection than seen in untreated mice. The polyacryl starch microparticles were effective as an adjuvant with secreted proteins, but did not potentiate the immune response in the study using flagellin.

Confocal laser-scanning and transmission electron microscopy demonstrated that the microparticles were taken up by pig respiratory nasal mucosa mounted in horizontal Ussing chambers. Although anticytokeratin 18 stained mucus-producing cells, M cells were not seen in the studied area.

Changing the route of administration of the microparticles conjugated with serum albumin can cause differences in the IgG-subclass ratios. The mucosal immune response measured as specific s-IgA levels, was induced by oral but not parenteral immunisation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2003. , p. 84
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 292
Keywords [en]
Pharmaceutics, mucosal vaccination, polyacryl starch microparticles, salmonella enteritidis, flagellin, fimbriae, rCTB, LPS, Ussing chamber
Keywords [sv]
Galenisk farmaci
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutics
Identifiers
URN: urn:nbn:se:uu:diva-3493ISBN: 91-554-5651-0 (print)OAI: oai:DiVA.org:uu-3493DiVA, id: diva2:163028
Public defence
2003-06-06, Lecture hall B21, BMC, Uppsala, 10:15
Opponent
Supervisors
Available from: 2003-05-14 Created: 2003-05-14 Last updated: 2018-01-13Bibliographically approved
List of papers
1. Extracellular antigens from Salmonella enteritidis induce effective immune response in mice after oral vaccination
Open this publication in new window or tab >>Extracellular antigens from Salmonella enteritidis induce effective immune response in mice after oral vaccination
2002 In: Infection and Immunity, ISSN 0019-9567, Vol. 70, no 3, p. 1434-1442Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90606 (URN)
Available from: 2003-05-14 Created: 2003-05-14Bibliographically approved
2. Uptake of ovalbumin-conjugated starch microparticles by pig respiratory nasal mucosa in vitro
Open this publication in new window or tab >>Uptake of ovalbumin-conjugated starch microparticles by pig respiratory nasal mucosa in vitro
Show others...
2003 In: Journal of Drug Targeting, ISSN 1061-186, Vol. 11, no 1, p. 75-82Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90607 (URN)
Available from: 2003-05-14 Created: 2003-05-14Bibliographically approved
3. Mucosal immunization with purified flagellin from Salmonella induces systemic and mucosal immune responses in C3H/HeJ mice
Open this publication in new window or tab >>Mucosal immunization with purified flagellin from Salmonella induces systemic and mucosal immune responses in C3H/HeJ mice
Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-90608 (URN)
Available from: 2003-05-14 Created: 2003-05-14Bibliographically approved
4. Immunogenic properties of the Salmonella atypical fimbriae in Balb/c mice
Open this publication in new window or tab >>Immunogenic properties of the Salmonella atypical fimbriae in Balb/c mice
Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-90609 (URN)
Available from: 2003-05-14 Created: 2003-05-14Bibliographically approved
5. Starch microparticles as an adjuvant in immunization: Effect of route of administration on the immune response in mice
Open this publication in new window or tab >>Starch microparticles as an adjuvant in immunization: Effect of route of administration on the immune response in mice
Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-90610 (URN)
Available from: 2003-05-14 Created: 2003-05-14 Last updated: 2010-01-13Bibliographically approved

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