{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:29:19Z","timestamp":1793320159325,"version":"4.5.0"},"reference-count":66,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T00:00:00Z","timestamp":1609200000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>Development of an effective vaccine against the leading human bacterial pathogen group A <jats:italic toggle=\"yes\">Streptococcus<\/jats:italic> (GAS) is a public health priority. The species defining group A cell wall carbohydrate (GAC, Lancefield antigen) can be engineered to remove its immunodominant <jats:italic toggle=\"yes\">N<\/jats:italic>-acetylglucosamine (GlcNAc) side chain, implicated in provoking autoimmune cross-reactivity in rheumatic heart disease, leaving its polyrhamnose core (GAC<jats:sup>PR<\/jats:sup>). Here we generate a novel protein conjugate of the GAC<jats:sup>PR<\/jats:sup> and test the utility of this conjugate antigen in active immunization. Instead of conjugation to a standard carrier protein, we selected SpyAD, a highly conserved GAS surface protein containing both B-cell and T-cell epitopes relevant to the bacterium that itself shows promise as a vaccine antigen. SpyAD was synthesized using the XpressTM cell-free protein expression system, incorporating a non-natural amino acid to which GAC<jats:sup>PR<\/jats:sup> was conjugated by site-specific click chemistry to yield high molecular mass SpyAD-GAC<jats:sup>PR<\/jats:sup> conjugates and avoid disruption of important T-cell and B-cell immunological epitopes. The conjugated SpyAD-GAC<jats:sup>PR<\/jats:sup> elicited antibodies that bound the surface of multiple GAS strains of diverse M types and promoted opsonophagocytic killing by human neutrophils. Active immunization of mice with a multivalent vaccine consisting of SpyAD-GAC<jats:sup>PR<\/jats:sup>, together with candidate vaccine antigens streptolysin O and C5a peptidase, protected against GAS challenge in a systemic infection model and localized skin infection model, without evidence of cross reactivity to human heart or brain tissue epitopes. This general approach may allow GAC to be safely and effectively included in future GAS subunit vaccine formulations with the goal of broad protection without autoreactivity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/im9.0000000000000044","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T22:49:31Z","timestamp":1609973371000},"page":"87-100","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":48,"title":["Site-Specific Conjugation of Cell Wall Polyrhamnose to Protein SpyAD Envisioning a Safe Universal Group A Streptococcal Vaccine"],"prefix":"10.1097","volume":"3","author":[{"given":"Nina J.","family":"Gao","sequence":"first","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Uchiyama","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Pill","sequence":"additional","affiliation":[{"name":"Vaxcyte, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Dahesh","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Olson","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Bautista","sequence":"additional","affiliation":[{"name":"Vaxcyte, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Maroju","sequence":"additional","affiliation":[{"name":"Vaxcyte, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aym","family":"Berges","sequence":"additional","affiliation":[{"name":"Vaxcyte, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet Z.","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond H.","family":"Zurich","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina M.","family":"van Sorge","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands"},{"name":"Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Fairman","sequence":"additional","affiliation":[{"name":"Vaxcyte, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Kapoor","sequence":"additional","affiliation":[{"name":"Vaxcyte, Inc., Foster City, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Nizet","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego, La Jolla, California, USA"},{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,6]]},"reference":[{"issue":"(11)","key":"R1-20250805","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S1473-3099(05)70267-X","article-title":"The global burden of group A streptococcal diseases","volume":"5","author":"Carapetis","year":"2005","journal-title":"Lancet Infect Dis"},{"issue":"(9)","key":"R2-20250805","doi-asserted-by":"crossref","first-page":"e422","DOI":"10.1111\/apa.13072","article-title":"A regionwide intervention to promote appropriate antibiotic use in children reversed trends in 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