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dc.contributor.authorOzberk, V
dc.contributor.authorReynolds, S
dc.contributor.authorHuo, Y
dc.contributor.authorCalcutt, A
dc.contributor.authorEskandari, S
dc.contributor.authorDooley, J
dc.contributor.authorMills, JL
dc.contributor.authorRasmussen, IS
dc.contributor.authorDietrich, J
dc.contributor.authorPandey, M
dc.contributor.authorGood, MF
dc.date.accessioned2021-03-09T00:54:32Z
dc.date.available2021-03-09T00:54:32Z
dc.date.issued2021
dc.identifier.issn2161-2129
dc.identifier.doi10.1128/mBio.03537-20
dc.identifier.urihttp://hdl.handle.net/10072/402971
dc.description.abstractInfections with Streptococcus pyogenes and their sequelae are responsi-ble for an estimated 18 million cases of serious disease with >700 million new primary cases and 500,000 deaths per year. Despite the burden of disease, there is currently no vaccine available for this organism. Here, we define a combination vaccine P*17/K4S2 comprising of 20-mer B-cell peptide epitopes, p*17 (a mutant derived from the highly conserved C3-repeat region of the M-protein), and K4S2 (derived from the streptococcal anti-neutrophil factor, Spy-CEP). The peptides are chemically conjugated to either diphtheria toxoid (DT) or a nontoxic mutant form of diphtheria toxin, CRM197. We demonstrate that a prime-pull immunization regimen involving two intramuscular inoculations with P*17/K4S2 adjuvanted with a two-component liposomal adjuvant system (CAF01; developed by Statens Serum Institut [SSI], Denmark), followed by an intranasal inoculation of unadju-vanted vaccine (in Tris) induces peptide-and S. pyogenes-binding antibodies and protects from mucosal and skin infection with hypervirulent covR/S mutant organisms. Prior vaccination with DT does not diminish the response to the conjugate peptide vaccines. Detailed Good Laboratory Practice (GLP) toxicological evaluation in male and female rats did not reveal any gross or histopathological adverse effects. IMPORTANCE A vaccine to control S. pyogenes infection is desperately warranted. S. pyogenes colonizes the upper respiratory tract (URT) and skin, from where it can progress to invasive and immune-mediated diseases. Global mortality estimates for S. pyogenes-associated diseases exceeds 500,000 deaths per year. S. pyogenes utilizes anti-genic variation as a defense mechanism to circumvent host immune responses and thus a successful vaccine needs to provide strain-transcending and multicompartment (mucosal and skin) immunity. By defining highly conserved and protective epitopes from two critical virulence factors (M-protein and Spy-CEP) and combining them with a potent immunostimulant, CAF®01, we are addressing an unmet clinical need for a muco-sally and skin-active subunit vaccine. We demonstrate that prime-pull immunization (2x intramuscular injections followed by intranasal immunization) promotes high sustained antibody levels in the airway mucosa and serum and protects against URT and invasive disease.
dc.description.peerreviewedYes
dc.languageen
dc.publisherAmerican Society for Microbiology
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto15
dc.relation.ispartofissue1
dc.relation.ispartofjournalmBio
dc.relation.ispartofvolume12
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchcode3107
dc.titlePrime-pull immunization with a bivalent m-protein and spy-cep peptide vaccine adjuvanted with caf®01 liposomes induces both mucosal and peripheral protection from covr/s mutant streptococcus pyogenes
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationOzberk, V; Reynolds, S; Huo, Y; Calcutt, A; Eskandari, S; Dooley, J; Mills, JL; Rasmussen, IS; Dietrich, J; Pandey, M; Good, MF, Prime-pull immunization with a bivalent m-protein and spy-cep peptide vaccine adjuvanted with caf®01 liposomes induces both mucosal and peripheral protection from covr/s mutant streptococcus pyogenes, mBio, 2021, 12 (1), pp. 1-15
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/
dc.date.updated2021-03-09T00:46:59Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2021 Ozberk et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorEskandari, Sherry
gro.griffith.authorPandey, Manisha
gro.griffith.authorReynolds, Simone
gro.griffith.authorOzberk, Victoria
gro.griffith.authorCalcutt, Ainslie M.
gro.griffith.authorDooley, Jessica L.
gro.griffith.authorGood, Michael F.
gro.griffith.authorHuo, Yongbao
gro.griffith.authorMills, Jamie S.


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