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dc.contributor.authorEskandari, Sharareh
dc.contributor.authorPattinson, David J
dc.contributor.authorStephenson, Rachel J
dc.contributor.authorGroves, Penny L
dc.contributor.authorApte, Simon H
dc.contributor.authorSedaghat, Bita
dc.contributor.authorChandurudu, Saranya
dc.contributor.authorDoolan, Denise L
dc.contributor.authorToth, Istvan
dc.date.accessioned2019-05-29T13:14:12Z
dc.date.available2019-05-29T13:14:12Z
dc.date.issued2018
dc.identifier.issn0947-6539
dc.identifier.doi10.1002/chem.201801378
dc.identifier.urihttp://hdl.handle.net/10072/382168
dc.description.abstractAdjuvant development and understanding the physicochemical properties of particles and interpreting the subsequent immunological responses is a challenge faced by many researchers in the vaccine field. We synthesized and investigated the physicochemical properties and immunogenicity of a library of multiple epitope self‐adjuvant lipopeptides in a novel asymmetric arrangement. Vaccine candidates were synthesized using a combination of solid‐phase peptide synthesis and copper‐mediated click chemistry. In vivo studies showed that vaccine constructs containing a single OVA CD8+ T‐cell epitope and two N‐terminally located C16 lipid moieties were more effective at generating robust cellular immune responses compared to the same molecule containing multiple copies of the OVA CD8+ T‐cell epitope with or without the C16 moieties. Furthermore, attachment of the two C16 lipids to the N‐terminus provoked formation of long β‐sheet fibrils and was shown to induce a higher CD8+ donor T‐cell frequency and IFN‐γ secretion, compared to vaccine constructs with an internal lipid placement. A regression analysis indicated that particle secondary structure had a significant impact on CD8+ donor T‐cell frequency and cytolytic activity. In addition, IFN‐γ production was influenced significantly by particle shape. The findings of this research will impact the future design of a vaccine intended to elicit cellular immune responses.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherWiley
dc.publisher.placeGermany
dc.relation.ispartofpagefrom9892
dc.relation.ispartofpageto9902
dc.relation.ispartofissue39
dc.relation.ispartofjournalChemistry - A European Journal
dc.relation.ispartofvolume24
dc.subject.fieldofresearchChemical Sciences not elsewhere classified
dc.subject.fieldofresearchChemical Sciences
dc.subject.fieldofresearchcode039999
dc.subject.fieldofresearchcode03
dc.titleInfluence of Physicochemical Properties of Lipopeptide Adjuvants on the Immune Response: A Rationale for Engineering a Potent Vaccine
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionPost-print
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article: PUBTITLE, Chemistry - A European Journal, Publication cover image Volume24, Issue39, 2018 which has been published in final form at https://doi.org/10.1002/chem.201801378. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html)
gro.hasfulltextFull Text
gro.griffith.authorEskandari, Sharareh


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