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dc.contributor.authorPandey, Manisha
dc.contributor.authorPowell, Jessica
dc.contributor.authorCalcutt, Ainslie
dc.contributor.authorZaman, Mehfuz
dc.contributor.authorPhillips, Zachary N
dc.contributor.authorHo, Mei Fong
dc.contributor.authorBatzloff, Michael R
dc.contributor.authorGood, Michael F
dc.date.accessioned2018-03-13T04:53:08Z
dc.date.available2018-03-13T04:53:08Z
dc.date.issued2017
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/s41598-017-14157-7
dc.identifier.urihttp://hdl.handle.net/10072/371109
dc.description.abstractGlobally, group A streptococcal infections are responsible for over 500,000 deaths per year. A safe vaccine that does not induce autoimmune pathology and that affords coverage for most GAS serotypes is highly desired. We have previously demonstrated that a vaccine based on the conserved M-protein epitope, J8 was safe and immunogenic in a pilot Phase I study. We subsequently improved vaccine efficacy by incorporation of a B-cell epitope from the IL-8 protease, SpyCEP, which protected IL-8 and enhanced neutrophil ingress to the site of infection. We have now substituted the carrier protein, diphtheria toxoid with its superior analogue, CRM197 which provides better immunogenicity and is widely used in licenced human vaccines. The new vaccine was compared with the DT conjugate vaccine to confirm that these modifications have not altered the physicochemical properties of the vaccine. This vaccine, when tested in an animal model of GAS infection, demonstrated significant reduction in systemic and local GAS burden, with comparable efficacy to the DT conjugate vaccine. The vaccine was shown to be equally effective in the presence of human plasma and in the presence of pre-existing DT-specific antibodies, thus minimising concerns regarding its potential efficacy in humans.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofpagefrom13786-1
dc.relation.ispartofpageto13786-11
dc.relation.ispartofjournalScientific Reports
dc.relation.ispartofvolume7
dc.subject.fieldofresearchMicrobiology not elsewhere classified
dc.subject.fieldofresearchcode060599
dc.titlePhysicochemical characterisation, immunogenicity and protective efficacy of a lead streptococcal vaccine: progress towards Phase I trial
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
gro.hasfulltextFull Text
gro.griffith.authorBatzloff, Michael R.
gro.griffith.authorPandey, Manisha
gro.griffith.authorGood, Michael F.
gro.griffith.authorDooley, Jessica L.
gro.griffith.authorZaman, Mehfuz
gro.griffith.authorCalcutt, Ainslie M.
gro.griffith.authorHo, Mei Fong
gro.griffith.authorPhillips, Zachary N.


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