{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T12:13:17Z","timestamp":1788437597194,"version":"build-2803163510"},"reference-count":53,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020955","name":"GlaxoSmithKline Biologicals","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100020955","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Capsular polysaccharides are the principal constituents of S. pneumoniae capsules and major determinants of bacterial virulence. As key antigenic targets, they represent the foundation for pneumococcal vaccine development. Cell wall polysaccharides (CWPSs) commonly persist as a process-related impurity during fermentation and purification and therefore require reliable quantification throughout vaccine manufacturing. In this work, a multinuclear quantitative NMR strategy based on 1H and 31P detection was developed for the determination of CWPSs in purified pneumococcal polysaccharide preparations. The analytical workflow was evaluated using a representative panel of ten pneumococcal serotypes selected to encompass different polysaccharide structural classes, charge characteristics, and CWPS variants. Both NMR methods were demonstrated to be fit for the purpose, exhibiting specificity, linearity, and accuracy across the investigated concentration range. The complementary use of 1H NMR and 31P NMR enabled reliable CWPS quantification while providing additional structural information and discrimination between CWPS variants. The proposed multinuclear NMR approach represents a robust, selective, and quantitative analytical platform for monitoring CWPS impurities during pneumococcal polysaccharide vaccine development and quality control.<\/jats:p>","DOI":"10.1021\/acsomega.6c06554","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:26:42Z","timestamp":1787070402000},"page":"51905-51920","source":"Crossref","is-referenced-by-count":0,"title":["A Multinuclear 1H and 31P NMR\nApproach for Quantification of Pneumococcal Cell-Wall Polysaccharide\nin Vaccine Development"],"prefix":"10.1021","volume":"11","author":[{"given":"Maria Concetta","family":"Forgione","sequence":"first","affiliation":[{"name":"GSK , Via Fiorentina 1 , ,","place":["Siena, Italy, 53100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccolo\u0300","family":"Maccari","sequence":"additional","affiliation":[{"name":"University of Siena , , Policlinico Santa Maria alle Scotte, Viale Mario Bracci 16 , ,","place":["Siena, Italy, 53100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Bonechi","sequence":"additional","affiliation":[{"name":"University of Siena , , Via Aldo Moro 2 , ,","place":["Siena, Italy, 53100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Carels","sequence":"additional","affiliation":[{"name":"GSK , 20 Avenue Fleming , ,","place":["Wavre, Belgium, 1300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Leroy","sequence":"additional","affiliation":[{"name":"GSK , Via Fiorentina 1 , ,","place":["Siena, Italy, 53100"]},{"name":"GSK , 20 Avenue Fleming , ,","place":["Wavre, Belgium, 1300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4906-5644","authenticated-orcid":true,"given":"Francesco","family":"Berti","sequence":"additional","affiliation":[{"name":"GSK , Via Fiorentina 1 , ,","place":["Siena, Italy, 53100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Biagini","sequence":"additional","affiliation":[{"name":"GSK , Via Fiorentina 1 , ,","place":["Siena, Italy, 53100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4298-9534","authenticated-orcid":true,"given":"Silvia","family":"Martini","sequence":"additional","affiliation":[{"name":"GSK , Via Fiorentina 1 , ,","place":["Siena, Italy, 53100"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"2026090307181977300_cit1","doi-asserted-by":"crossref","DOI":"10.1093\/hesc\/9780199270293.001.0001","volume-title":"Organic chemistry","author":"Clayden","year":"2012"},{"key":"2026090307181977300_cit2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1159\/000081689","article-title":"Capsular polysaccharides and their role in virulence","volume":"12","author":"Taylor","year":"2005","journal-title":"Contrib. 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Rep."},{"key":"2026090307181977300_cit6","doi-asserted-by":"publisher","first-page":"5695","DOI":"10.1073\/pnas.1620431114","article-title":"Streptococcus pneumoniae capsular\npolysaccharide is linked to peptidoglycan via a direct glycosidic\nbond to beta-D-N-acetylglucosamine","volume":"114","author":"Larson","year":"2017","journal-title":"Proc. Natl.\nAcad. Sci. U. S. A."},{"key":"2026090307181977300_cit7","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1128\/microbiolspec.gpp3-0004-2018","article-title":"Streptococcus pneumoniae: Invasion and Inflammation","volume":"7","author":"Loughran","year":"2019","journal-title":"Microbiol. Spectrum."},{"key":"2026090307181977300_cit8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1084\/jem.54.1.51","article-title":"Decomposition of\nthe Capsular Polysaccharide of Pneumococcus\nType III by a Bacterial Enzyme","volume":"54","author":"Dubos","year":"1931","journal-title":"J. Exp. 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Biochem."},{"key":"2026090307181977300_cit30","doi-asserted-by":"publisher","first-page":"469","DOI":"10.3390\/vaccines12050469","article-title":"Identification\nand Quantification of a Pneumococcal\nCell Wall Polysaccharide by Antibody-Enhanced Chromatography Assay","volume":"12","author":"Deng","year":"2024","journal-title":"Vaccines"},{"key":"2026090307181977300_cit31","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jpba.2014.05.004","article-title":"Exploring the Group\nB Streptococcus capsular polysaccharides: the\nstructural diversity provides the basis for development of NMR-based\nidentity assays","volume":"98","author":"Pinto","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"2026090307181977300_cit32","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/978-1-4939-2874-3_12","article-title":"Characterization\nof Carbohydrate Vaccines by NMR Spectroscopy","volume":"1331","author":"Berti","year":"2015","journal-title":"Methods Mol. 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Biomed.\nAnal."},{"key":"2026090307181977300_cit41","volume-title":"Protein\nNMR Spectroscopy: Principles and Practice","author":"Cavanagh","year":"2007","edition":"2nd"},{"issue":"3","key":"2026090307181977300_cit42","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1046\/j.1432-1327.1999.00835.x","article-title":"The pneumococcal common antigen C-polysaccharide\noccurs in different forms. Mono-substituted or di-substituted with\nphosphocholine","volume":"265","author":"Karlsson","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"2026090307181977300_cit43","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1046\/j.1432-1327.1998.2550296.x","article-title":"The chemical structures of the capsular\npolysaccharides from Streptococcus pneumoniae types\n32F and 32A","volume":"255","author":"Karlsson","year":"1998","journal-title":"Eur. J. 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Soc."},{"key":"2026090307181977300_cit51","doi-asserted-by":"publisher","first-page":"5246","DOI":"10.3390\/app15105246","article-title":"Revealing\nthe Complexity of Polysaccharides: Advances\nin NMR Spectroscopy for Structural Elucidation and Functional Characterization","volume":"15","author":"Liu","year":"2025","journal-title":"Appl. Sci."},{"key":"2026090307181977300_cit52","doi-asserted-by":"publisher","first-page":"6304","DOI":"10.1021\/acs.analchem.9b05107","article-title":"Development of a Specific\nand Sensitive\nHPAEC-PAD Method for Quantification of Vi Polysaccharide Applicable\nto Other Polysaccharides Containing Amino Uronic Acids","volume":"92","author":"Giannelli","year":"2020","journal-title":"Anal. 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