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dc.contributor.authorRivera-Hernandez, Tania
dc.contributor.authorCarnathan, Diane G
dc.contributor.authorJones, Scott
dc.contributor.authorCork, Amanda J
dc.contributor.authorDavies, Mark R
dc.contributor.authorMoyle, Peter M
dc.contributor.authorToth, Istvan
dc.contributor.authorBatzloff, Michael R
dc.contributor.authorMcCarthy, James
dc.contributor.authorNizet, Victor
dc.contributor.authorGoldblatt, David
dc.contributor.authorSilvestri, Guido
dc.contributor.authorWalker, Mark J
dc.date.accessioned2021-04-13T01:50:43Z
dc.date.available2021-04-13T01:50:43Z
dc.date.issued2019
dc.identifier.issn2150-7511en_US
dc.identifier.doi10.1128/mBio.00693-19en_US
dc.identifier.urihttp://hdl.handle.net/10072/403677
dc.description.abstractGroup A Streptococcus (GAS) infections account for an estimated 500,000 deaths every year. This bacterial pathogen is responsible for a variety of mild and life-threatening infections and the triggering of chronic autoimmune sequelae. Pharyngitis caused by group A Streptococcus (GAS), but not asymptomatic GAS carriage, is a prerequisite for acute rheumatic fever (ARF). Repeated bouts of ARF may trigger rheumatic heart disease (RHD), a major cause of heart failure and stroke accounting for 275,000 deaths annually. A vaccine that prevents pharyngitis would markedly reduce morbidity and mortality from ARF and RHD. Nonhuman primates (NHPs) have been utilized to model GAS diseases, and experimentally infected rhesus macaques develop pharyngitis. Here we use an NHP model of GAS pharyngitis to evaluate the efficacy of an experimental vaccine, Combo5 (arginine deiminase [ADI], C5a peptidase [SCPA], streptolysin O [SLO], interleukin-8 [IL-8] protease [SpyCEP], and trigger factor [TF]), specifically designed to exclude GAS components potentially linked to autoimmune complications. Antibody responses against all Combo5 antigens were detected in NHP serum, and immunized NHPs showed a reduction in pharyngitis and tonsillitis compared to controls. Our work establishes the NHP model as a gold standard for the assessment of GAS vaccines. IMPORTANCE GAS-related diseases disproportionally affect disadvantaged populations (e.g., indigenous populations), and development of a vaccine has been neglected. A recent strong advocacy campaign driven by the World Health Organization and the International Vaccine Institute has highlighted the urgent need for a GAS vaccine. One significant obstacle in GAS vaccine development is the lack of a widely used animal model to assess vaccine efficacy. Researchers in the field use a wide range of murine models of infection and in vitro assays, sometimes yielding conflicting results. Here we present the nonhuman primate pharyngeal infection model as a tool to assess vaccine-induced protection against colonization and clinical symptoms of pharyngitis and tonsillitis. We have tested the efficacy of an experimental vaccine candidate with promising results. We believe that the utilization of this valuable tool by the GAS vaccine research community could significantly accelerate the realization of a safe and effective GAS vaccine for humans.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherAMER SOC MICROBIOLOGYen_US
dc.relation.ispartofpagefrome00693-19en_US
dc.relation.ispartofissue2en_US
dc.relation.ispartofjournalmBioen_US
dc.relation.ispartofvolume10en_US
dc.subject.fieldofresearchMicrobiologyen_US
dc.subject.fieldofresearchcode0605en_US
dc.subject.keywordsScience & Technologyen_US
dc.subject.keywordsLife Sciences & Biomedicineen_US
dc.subject.keywordsStreptococcus pyogenesen_US
dc.subject.keywordsgroup A Streptococcusen_US
dc.titleAn Experimental Group A Streptococcus Vaccine That Reduces Pharyngitis and Tonsillitis in a Nonhuman Primate Modelen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Articlesen_US
dcterms.bibliographicCitationRivera-Hernandez, T; Carnathan, DG; Jones, S; Cork, AJ; Davies, MR; Moyle, PM; Toth, I; Batzloff, MR; McCarthy, J; Nizet, V; Goldblatt, D; Silvestri, G; Walker, MJ, An Experimental Group A Streptococcus Vaccine That Reduces Pharyngitis and Tonsillitis in a Nonhuman Primate Model, mBio, 2019, 10 (2), pp. e00693-19en_US
dcterms.licensehttps://creativecommons.org/licenses/by/4.0/en_US
dc.date.updated2021-04-11T23:48:25Z
dc.description.versionVersion of Record (VoR)en_US
gro.rights.copyright© 2019 Rivera-Hernandez 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.en_US
gro.hasfulltextFull Text
gro.griffith.authorBatzloff, Michael R.


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