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dc.contributor.authorPandey, M
dc.contributor.authorCalcutt, A
dc.contributor.authorOzberk, V
dc.contributor.authorChen, Z
dc.contributor.authorCroxen, M
dc.contributor.authorPowell, J
dc.contributor.authorLangshaw, E
dc.contributor.authorMills, JL
dc.contributor.authorJen, FEC
dc.contributor.authorMcCluskey, J
dc.contributor.authorRobson, J
dc.contributor.authorTyrrell, GJ
dc.contributor.authorGood, MF
dc.date.accessioned2019-12-12T00:42:14Z
dc.date.available2019-12-12T00:42:14Z
dc.date.issued2019
dc.identifier.issn2375-2548
dc.identifier.doi10.1126/sciadv.aax3013
dc.identifier.urihttp://hdl.handle.net/10072/389698
dc.description.abstractInvasive streptococcal disease (ISD) and toxic shock syndrome (STSS) result in over 160,000 deaths each year. We modelled these in HLA-transgenic mice infected with a clinically lethal isolate expressing Streptococcal pyrogenic exotoxin (Spe) C and demonstrate that both SpeC and streptococcal M protein, acting cooperatively, are required for disease. Vaccination with a conserved M protein peptide, J8, protects against STSS by causing a dramatic reduction in bacterial burden associated with the absence of SpeC and inflammatory cytokines in the blood. Furthermore, passive immunotherapy with antibodies to J8 quickly resolves established disease by clearing the infection and ablating the inflammatory activity of the M protein, which is further enhanced by addition of SpeC antibodies. Analysis of 77 recent isolates of Streptococcus pyogenes causing ISD, demonstrated that anti-J8 antibodies theoretically recognize at least 73, providing strong support for using antibodies to J8, with or without antibodies to SpeC, as a therapeutic approach.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherAmerican Association for the Advancement of Science
dc.publisher.placeUnited States
dc.relation.ispartofpagefromeaax3013: 1
dc.relation.ispartofpagetoeaax3013: 11
dc.relation.ispartofissue9
dc.relation.ispartofjournalScience Advances
dc.relation.ispartofvolume5
dc.subject.fieldofresearchClinical Sciences
dc.subject.fieldofresearchcode1103
dc.subject.keywordsScience & Technology
dc.subject.keywordsMultidisciplinary Sciences
dc.subject.keywordsScience & Technology - Other Topics
dc.subject.keywordsINTRAVENOUS IMMUNOGLOBULIN
dc.subject.keywordsPYROGENIC EXOTOXIN
dc.titleAntibodies to the conserved region of the M protein and a streptococcal superantigen cooperatively resolve toxic shock-like syndrome in HLA-humanized mice
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationPandey, M; Calcutt, A; Ozberk, V; Chen, Z; Croxen, M; Powell, J; Langshaw, E; Mills, JL; Jen, FEC; McCluskey, J; Robson, J; Tyrrell, GJ; Good, MF, Antibodies to the conserved region of the M protein and a streptococcal superantigen cooperatively resolve toxic shock-like syndrome in HLA-humanized mice, Science Advances, 2019, 5 (9), pp. eaax3013: 1-eaax3013: 11
dcterms.dateAccepted2019-08-07
dcterms.licensehttp://creativecommons.org/licenses/by-nc/4.0/
dc.date.updated2019-12-12T00:40:28Z
dc.description.versionPublished
gro.rights.copyright© 2019 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorGood, Michael F.
gro.griffith.authorJen, Freda E.
gro.griffith.authorPandey, Manisha
gro.griffith.authorOzberk, Victoria
gro.griffith.authorCalcutt, Ainslie M.
gro.griffith.authorLangshaw, Emma
gro.griffith.authorMills, Jamie-Lee S.


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