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Oral vaccination against diphtheria using starch microparticles as adjuvant in man
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-92285OAI: oai:DiVA.org:uu-92285DiVA: diva2:165301
Available from: 2004-11-04 Created: 2004-11-04 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Development of a New Oral Vaccine against Diphtheria and the Study of its Immunogenicity in Mouse and Man
Open this publication in new window or tab >>Development of a New Oral Vaccine against Diphtheria and the Study of its Immunogenicity in Mouse and Man
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Most pathogens enter the body via mucosal surfaces. In contrast to parenterally administered vaccination, mucosal vaccination has the advantage of eliciting both a systemic and a local mucosal immune response. An oral biodegradable adjuvant with these features would have great potential.

This thesis has focused on the development of a new oral vaccine against diphtheria. Biodegradable polyacryl starch microparticles were used as a mucosal adjuvant. Diphtheria toxin or cross-reacting material of diphtheria toxin (CRM197) was covalently conjugated to the microparticles and fed to mice by oral gavage. Formaldehyde treatment was also studied as a means of either detoxifying (diphtheria toxin) or stabilising (CRM197) these formulations. All formulations given to mice orally or parenterally, but not intranasally, induced a strong systemic immune response and diphtheria toxin neutralising antibodies. Only formulations administered orally induced a mucosal IgA response as well.

The non-toxic recombinant protein CRM197 proved to be a promising antigen candidate in an oral diphtheria vaccine when conjugated to the microparticles. Mild treatment of CRM197 with formaldehyde before conjugation to the starch microparticles potentiated the immunogenicity of the formulation. However, no immune response was detected in healthy volunteers after administration of this vaccine in a phase I trial. The possible reasons for the difference in response between mouse and man are discussed.

The use of cDNA expression macro array technology was also evaluated as a tool in vaccine-related research. Tetanus toxoid and aluminium phosphate were used as model parenteral antigen and adjuvant. It was concluded that the antigen modulates the molecular mechanisms of the aluminium phosphate adjuvant to a greater extent than previously recognised.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 54 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 315
Keyword
Pharmaceutics, oral vaccination, mucosal vaccination, diphtheria, biodegradable, microparticles, starch, CRM197, adjuvant, vaccine, Galenisk farmaci
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-4629 (URN)91-554-6069-0 (ISBN)
Public defence
2004-12-03, B41, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-11-04 Created: 2004-11-04Bibliographically approved

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