{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:21:48Z","timestamp":1790022108101,"version":"4.0.1"},"reference-count":44,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T00:00:00Z","timestamp":1737763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GlaxoSmithKline Biologicals SA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Typhoid and paratyphoid fevers represent a global health burden, especially in Southern Asia, exacerbated by the increase in antimicrobial resistance. While vaccines against Salmonella Typhi have been successfully introduced, a vaccine against S. Paratyphi A is not available, yet. Efforts to develop an effective vaccine targeting both Salmonella serovars are currently ongoing. GVGH is developing a bivalent vaccine constituted by the Vi-CRM197 typhoid conjugate vaccine (TCV), and the Salmonella Paratyphi A O-antigen (O:2), also conjugated to the CRM197 carrier protein (O:2-CRM197). In this work we have characterized a panel of S. Paratyphi A clinical isolates from endemic regions, differing in terms of their O:2 structural features. Methods: Rabbits were immunized with the S. Paratyphi A component of the vaccine candidate and the resulting sera were tested for their ability to bind and kill the isolates using flow cytometry and luminescence-based serum bactericidal assay (L-SBA). Results: The O:2-CRM197 glycoconjugate induced a functional immune response in rabbits, effectively binding and killing a diverse panel of clinical isolates. The sera demonstrated bactericidal activity independent of the O:2 structural variations, including differences in O-acetylation and glucosylation levels. Additionally, the study found that the O:2-CRM197 conjugate\u2019s adsorption to Alhydrogel did not significantly impact its immunogenicity or bactericidal efficacy. Conclusions: The O:2-CRM197 component of the bivalent vaccine candidate shows promise in providing broad protection against S. Paratyphi A isolates, regardless of their O-antigen structural variations. The ongoing clinical studies on human sera are expected to confirm these results.<\/jats:p>","DOI":"10.3390\/vaccines13020122","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T03:54:27Z","timestamp":1737950067000},"page":"122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Salmonella Paratyphi A O-Antigen Glycoconjugate Vaccine Is Able to Induce Antibodies with Bactericidal Activity Against a Panel of Clinical Isolates"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4088-0483","authenticated-orcid":false,"given":"Marika","family":"Pinto","sequence":"first","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH), via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Durante","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH), via Fiorentina 1, 53100 Siena, Italy"},{"name":"GSK, via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6633-567X","authenticated-orcid":false,"given":"Martina","family":"Carducci","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH), via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Massai","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH), via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7103-0723","authenticated-orcid":false,"given":"Renzo","family":"Alfini","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH), via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2638-0713","authenticated-orcid":false,"given":"Elli","family":"Mylona","sequence":"additional","affiliation":[{"name":"Cambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhilasha","family":"Karkey","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Patan Academy of Health Sciences, P.O. Box 26500, Kathmandu 44700, Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Baker","sequence":"additional","affiliation":[{"name":"Cambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Micoli","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH), via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6112-6841","authenticated-orcid":false,"given":"Carlo","family":"Giannelli","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH), via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0170-1285","authenticated-orcid":false,"given":"Omar","family":"Rossi","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH), via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Rondini","sequence":"additional","affiliation":[{"name":"GSK Vaccines Institute for Global Health (GVGH), via Fiorentina 1, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,25]]},"reference":[{"key":"ref_1","unstructured":"(2019). 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