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dc.contributor.authorAbdel-Aal, Abu-Baker M.
dc.contributor.authorZaman, Mehfuz
dc.contributor.authorFujita, Yoshio
dc.contributor.authorBatzloff, Michael R.
dc.contributor.authorGood, Michael Francis
dc.contributor.authorToth, Istvan
dc.date.accessioned2011-07-14
dc.date.accessioned2017-03-01T21:59:23Z
dc.date.available2017-03-01T21:59:23Z
dc.date.issued2010
dc.date.modified2011-08-12T06:20:28Z
dc.identifier.issn0818-9641
dc.identifier.doihttp://dx.doi.org/10.1021/jm1007787
dc.identifier.urihttp://hdl.handle.net/10072/39929.1
dc.description.abstractImmunological assessment of group A streptococcal (GAS) branched lipopeptides demonstrated the impact of spatial arrangement of vaccine components on both the quality and quantity of their immune responses. Each lipopeptide was composed of three components: a GAS B-cell epitope (J14), a universal CD4+ T-cell helper epitope (P25), and an immunostimulant lipid moiety that differs only in its spatial arrangement. The best systemic immune responses were demonstrated by a lipopeptide featuring the lipid moiety at the lipopeptide C-terminus. However, this candidate did not achieve protection against bacterial challenge. The best protection (100%) was shown by a lipopeptide featuring a C-terminal J14, conjugated through a lysine residue to P25 at the N-terminus, and a lipid moiety on the lysine side chain. The former candidate features α-helical conformation required to produce protective J14-specific antibodies. Our results highlight the importance of epitope orientation and lipid position in the design of three-component synthetic vaccines.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.language.isoen_AU
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom8041
dc.relation.ispartofpageto8046
dc.relation.ispartofissue22
dc.relation.ispartofjournalJournal of Medicinal Chemistry
dc.relation.ispartofvolume53
dc.rights.retentionY
dc.subject.fieldofresearchImmunology not elsewhere classified
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchcode110799
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode1107
dc.titleDesign of Three-Component Vaccines against Group A Streptococcal Infections: Importance of Spatial Arrangement of Vaccine Components
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codec1x
gro.facultyFaculty of Science, Environment, Engineering and Technology
gro.date.issued2010
gro.hasfulltextNo Full Text
gro.griffith.authorGood, Michael F.


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