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dc.contributor.authorLAVELLE, EDWARD
dc.contributor.authorMILLS, KINGSTON
dc.date.accessioned2009-09-24T16:57:31Z
dc.date.available2009-09-24T16:57:31Z
dc.date.issued2004
dc.date.submitted2004en
dc.identifier.citationBowe, F., Lavelle, E.C., McNeela, E. A., Hale, C., Clare, S., Arico, B., Giuliani, M.M., Rae, A., Huett, A., Rappuoli, R., Dougan, G. and Mills, K. H.G. `Mucosal vaccination against serogroup B meningococcus: Induction of bactericidal antibodies and cellular immunity following intranasal immunization with NadA of Neisseria meningitidis and mutants of Escherichia coli heat-labile enterotoxin? in Infection and Immunity, 72, (7), 2004, pp 4052 - 4060en
dc.identifier.otherY
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/33232
dc.descriptionPUBLISHEDen
dc.description.abstractConjugated polysaccharide vaccines protect against serogroup C meningococci. However, this approach cannot be applied to serogroup B, which is still a major cause of meningitis. We evaluated the immunogenicity of three surface-exposed proteins from serogroup B Neisseria meningitidis (App, NhhA, and NadA) identified during whole-genome sequencing. Mice were immunized intranasally with individual proteins in the presence of wild-type Escherichia coli heat-labile enterotoxin (LTwt), LTR72, a partially inactivated mutant, or LTK63, a completely nontoxic mutant, as the adjuvant. Each of the meningococcal proteins induced significant cellular responses; NhhA and NadA induced strong antibody responses, but only NadA induced bactericidal antibody when administered intranasally with mucosal adjuvants. In addition, immunoglobulin A and bactericidal antibodies were detected in the respiratory tract following intranasal delivery of NadA. Analysis of antigen-specific cytokine production by T cells from immunized mice revealed that intranasal immunization with NadA alone failed to generate detectable cellular immune responses. In contrast, LTK63, LTR72, and LTwt significantly augmented NadA-specific gamma interferon, interleukin-4 (IL-4), IL-5, and IL-10 production by spleen and lymph node cells, suggesting that both Th1 and Th2 cells were induced in vivo. The strongest cellular responses and highest bactericidal antibody titers were generated with LTR72 as the adjuvant. These findings demonstrate that the quality and magnitude of the immune responses generated by mucosal vaccines are influenced by the antigen as well as the adjuvant and suggest that nasal delivery of NadA with mucosal adjuvants has considerable potential in the development of a mucosal vaccine against serogroup B meningococci.en
dc.description.sponsorshipThis work was supported by a grant from the European Commission within the 5th Framework Programme: Mucosal Immunization and Vaccine Development (MUCIMM), contract no. QLK2CT 1999 00228. K.H.G.M. and E.C.L. are supported by Science Foundation Ireland (grant no. 00/PI.I/B045). C.H. is supported by a NEOVAC grant from the European Commission, contract no. QLK2-CT-1999-00429en
dc.format.extent4052en
dc.format.extent4060en
dc.format.extent157164 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.relation.ispartofseriesInfection and Immunityen
dc.relation.ispartofseries72en
dc.relation.ispartofseries7en
dc.rightsYen
dc.subjectBiochemistryen
dc.titleMucosal vaccination against serogroup B meningococcus:Induction of bactericidal antibodies and cellular immunity following intranasal immunization with NadA of Neisseria meningitidis and mutants of Escherichia coli heat-labile enterotoxinen
dc.typeJournal Articleen
dc.contributor.sponsorEuropean Commission
dc.contributor.sponsorScience Foundation Ireland
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/millsk
dc.identifier.rssinternalid7764
dc.identifier.rssurihttp://dx.doi.org/10.1128/IAI.72.7.4052-4060.2004


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