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dc.contributor.authorMILLS, KINGSTON
dc.date.accessioned2009-09-28T13:17:17Z
dc.date.available2009-09-28T13:17:17Z
dc.date.issued2003
dc.date.submitted2003en
dc.identifier.citationMills, K.H.G., Cosgrove, C., McNeela E.A., Sexton, A., Giemza, R., Jabbal-Gill, I., Church, A., Lin, W., Illum, L., Podda, A., Rappuoli, R., Pizza, M. Griffin, G.E. and Lewis, D.J.M. `Protective levels of diphtheria-neutralizing antibody induced in healthy volunteers by unilateral priming-boosting intranasal immunization associated with restricted ipsilateral mucosal secretory immunoglobulin a? in Infection and Immunity, 71, (2), 2003, pp 726 - 732en
dc.identifier.otherY
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/33332
dc.descriptionPUBLISHEDen
dc.description.abstractSubunit intranasal vaccines offer the prospect of inducing combined systemic-mucosal immunity against mucosally transmitted infections such as human immunodeficiency virus. However, although human studies have demonstrated the induction of active immunity, secretory immunoglobulin A (sIgA) responses are variable, and no study has demonstrated protection by accepted vaccine-licensing criteria as measured by direct toxin-neutralizing activity. Using the genetically inactivated mutant diphtheria toxoid CRM197 in a bioadhesive polycationic polysaccharide chitosan delivery system, we found that a single nasal immunization was well tolerated and boosted antitoxin neutralizing activity in healthy volunteers, which could be further boosted by a second immunization. The neutralizing activity far exceeded accepted protective levels and was equivalent to that induced by standard intramuscular vaccine and significantly greater than intranasal immunization with CRM197 in the absence of chitosan. A striking but unexpected observation was that although unilateral intranasal immunization induced circulating antitoxin antibody-secreting cells, a nasal antitoxin sIgA response was seen only after the second immunization and only in the vaccinated nostril. If these data are reproduced in larger studies, an intranasal diphtheria vaccine based on CRM197-chitosan could be rapidly licensed for human use. However, a restricted sIgA response suggests that care must be taken in the priming-boosting strategy and clinical sampling techniques when evaluating such vaccines for the induction of local mucosal immunity.en
dc.description.sponsorshipC. Cosgrove is supported by Wellcome Trust Programme Grant 043139. E. McNeela is supported by the European Union (EU) Fifth Framework Mucosal Immunization programs MUCADJ (contract no. QLK2 CT 1999 00070) and (with A. Sexton) MUCIMM (contract no. QLK2 CT 1999 00228)en
dc.format.extent726en
dc.format.extent732en
dc.format.extent121166 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.relation.ispartofseriesInfection and Immunityen
dc.relation.ispartofseries71en
dc.relation.ispartofseries2en
dc.rightsYen
dc.subjectBiochemistryen
dc.titleProtective levels of diphtheria-neutralizing antibody induced in healthy volunteers by unilateral priming-boosting intranasal immunization associated with restricted ipsilateral mucosal secretory immunoglobulin aen
dc.typeJournal Articleen
dc.contributor.sponsorWellcome Trust
dc.contributor.sponsorEuropean Union (EU)
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/millsk
dc.identifier.rssinternalid7750


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