{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:51:04Z","timestamp":1790009464378,"version":"4.0.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Vaccines"],"DOI":"10.1038\/s41541-025-01305-8","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T10:25:22Z","timestamp":1765621522000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of cross-functional antibody responses elicited by a four-component GMMA Shigella vaccine"],"prefix":"10.1038","volume":"10","author":[{"given":"Valentina","family":"Caradonna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanna","family":"Sarakinou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Di Benedetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Hunyady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usman","family":"Nakakana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Alfini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Boretto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Gemmellaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Ferruzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miren","family":"Iturriza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Berlanda Scorza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Rondini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentino","family":"Conti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Giannelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwani Kumar","family":"Arora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Micoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"1305_CR1","doi-asserted-by":"publisher","first-page":"e321","DOI":"10.1016\/S2214-109X(18)30483-2","volume":"7","author":"JD Anderson","year":"2019","unstructured":"Anderson, J. D. et al. Burden of enterotoxigenic Escherichia coli and shigella non-fatal diarrhoeal infections in 79 low-income and lower middle-income countries: a modelling analysis. Lancet Glob. Health 7, e321\u2013e330 (2019).","journal-title":"Lancet Glob. Health"},{"key":"1305_CR2","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/S0140-6736(17)33296-8","volume":"391","author":"KL Kotloff","year":"2018","unstructured":"Kotloff, K. L., Riddle, M. S., Platts-Mills, J. A., Pavlinac, P. & Zaidi, A. K. Shigellosis. Lancet 391, 801\u2013812 (2018).","journal-title":"Lancet"},{"key":"1305_CR3","unstructured":"World Health Organization. Guidelines for the control of shigellosis, including epidemics due to Shigella dysenteriae type 1. Geneva: World Health Organization; 2005."},{"key":"1305_CR4","unstructured":"World Health Organization. WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva: World Health Organization; 2024. Licence: CC BY-NC-SA 3.0 IGO."},{"key":"1305_CR5","unstructured":"Scott, T. A. et al. Shigella sonnei: epidemiology, evolution, pathogenesis, resistance and host interactions. Nature Reviews Microbiology, 1\u201315 (2024)."},{"key":"1305_CR6","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1093\/jac\/dkad031","volume":"78","author":"A Moreno-Mingorance","year":"2023","unstructured":"Moreno-Mingorance, A. et al. Increasing trend of antimicrobial resistance in Shigella associated with MSM transmission in Barcelona, 2020\u201321: outbreak of XRD Shigella sonnei and dissemination of ESBL-producing Shigella flexneri. J. Antimicrobial Chemother. 78, 975\u2013982 (2023).","journal-title":"J. Antimicrobial Chemother."},{"key":"1305_CR7","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/S1473-3099(22)00807-6","volume":"23","author":"K Thorley","year":"2023","unstructured":"Thorley, K. et al. Emergence of extensively drug-resistant and multidrug-resistant Shigella flexneri serotype 2a associated with sexual transmission among gay, bisexual, and other men who have sex with men, in England: a descriptive epidemiological study. Lancet Infect. Dis. 23, 732\u2013739 (2023).","journal-title":"Lancet Infect. Dis."},{"key":"1305_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25764-3","volume":"8","author":"KS Baker","year":"2018","unstructured":"Baker, K. S. et al. Genomic epidemiology of Shigella in the United Kingdom shows transmission of pathogen sublineages and determinants of antimicrobial resistance. Sci. Rep. 8, 7389 (2018).","journal-title":"Sci. Rep."},{"key":"1305_CR9","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s44259-024-00038-3","volume":"2","author":"LCE Mason","year":"2024","unstructured":"Mason, L. C. E. et al. The re-emergence of sexually transmissible multidrug resistant Shigella flexneri 3a, England, United Kingdom. NPJ Antimicrobials Resistance 2, 20 (2024).","journal-title":"NPJ Antimicrobials Resistance"},{"key":"1305_CR10","doi-asserted-by":"crossref","unstructured":"Cohen, D. et al. Twenty-five years of sentinel laboratory-based surveillance of shigellosis in a high-income country endemic for the disease, Israel, 1998 to 2022. Euro Surveill 29 (2024).","DOI":"10.2807\/1560-7917.ES.2024.29.31.2400022"},{"key":"1305_CR11","doi-asserted-by":"publisher","first-page":"e0003708","DOI":"10.1371\/journal.pntd.0003708","volume":"9","author":"CN Thompson","year":"2015","unstructured":"Thompson, C. N., Duy, P. T. & Baker, S. The Rising Dominance of Shigella sonnei: An Intercontinental Shift in the Etiology of Bacillary Dysentery. PLoS Negl. Trop. Dis. 9, e0003708 (2015).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"1305_CR12","doi-asserted-by":"publisher","first-page":"S66","DOI":"10.1093\/cid\/ciac969","volume":"76","author":"IN Kasumba","year":"2023","unstructured":"Kasumba, I. N. et al. Shigella in Africa: new insights from the Vaccine Impact on Diarrhea in Africa (VIDA) study. Clin. Infect. Dis. 76, S66\u2013S76 (2023).","journal-title":"Clin. Infect. Dis."},{"key":"1305_CR13","unstructured":"Meiring, S. et al. Germs-sa: annual surveillance review 2022-key findings."},{"key":"1305_CR14","unstructured":"European Centre for Disease Prevention and Control. Shigellosis. Annual Epidemiological Report for 2022, Stockholm. (2024)."},{"key":"1305_CR15","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1093\/cid\/ciu468","volume":"59","author":"S Livio","year":"2014","unstructured":"Livio, S. et al. Shigella isolates from the global enteric multicenter study inform vaccine development. Clin. Infect. Dis. 59, 933\u2013941 (2014).","journal-title":"Clin. Infect. Dis."},{"key":"1305_CR16","doi-asserted-by":"publisher","first-page":"e0011964","DOI":"10.1371\/journal.pntd.0011964","volume":"18","author":"P Bose","year":"2024","unstructured":"Bose, P. et al. Prevalence and changing antimicrobial resistance profiles of Shigella spp. isolated from diarrheal patients in Kolkata during 2011\u20132019. PLoS neglected tropical Dis. 18, e0011964 (2024).","journal-title":"PLoS neglected tropical Dis."},{"key":"1305_CR17","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1099\/jmm.0.032920-0","volume":"60","author":"S Ghosh","year":"2011","unstructured":"Ghosh, S. et al. Genetic characteristics and changing antimicrobial resistance among Shigella spp. isolated from hospitalized diarrhoeal patients in Kolkata, India. J. Med. Microbiol. 60, 1460\u20131466 (2011).","journal-title":"J. Med. Microbiol."},{"key":"1305_CR18","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1111\/j.1574-6976.2008.00114.x","volume":"32","author":"B Liu","year":"2008","unstructured":"Liu, B. et al. Structure and genetics of Shigella O antigens. FEMS Microbiol. Rev. 32, 627\u2013653 (2008).","journal-title":"FEMS Microbiol. Rev."},{"key":"1305_CR19","doi-asserted-by":"publisher","first-page":"e522","DOI":"10.5001\/omj.2023.65","volume":"38","author":"M Sadredinamin","year":"2023","unstructured":"Sadredinamin, M., Yazdansetad, S., Alebouyeh, M., Yazdi, M. M. K. & Ghalavand, Z. Shigella flexneri Serotypes: O-antigen Structure, Serotype Conversion, and Serotyping Methods. Oman Med. J. 38, e522 (2023).","journal-title":"Oman Med. J."},{"key":"1305_CR20","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1111\/j.1574-695X.2012.01000.x","volume":"66","author":"AV Perepelov","year":"2012","unstructured":"Perepelov, A. V. et al. Shigella flexneri O-antigens revisited: final elucidation of the O-acetylation profiles and a survey of the O-antigen structure diversity. FEMS Immunol. Med. Microbiol. 66, 201\u2013210 (2012).","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"1305_CR21","doi-asserted-by":"publisher","first-page":"e0009826","DOI":"10.1371\/journal.pntd.0009826","volume":"15","author":"F Citiulo","year":"2021","unstructured":"Citiulo, F. et al. Rationalizing the design of a broad coverage Shigella vaccine based on evaluation of immunological cross-reactivity among S. flexneri serotypes. PLoS Neglected Tropical Dis. 15, e0009826 (2021).","journal-title":"PLoS Neglected Tropical Dis."},{"key":"1305_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.715393","volume":"12","author":"F Mancini","year":"2021","unstructured":"Mancini, F. et al. GMMA-based vaccines: the known and the unknown. Front. Immunol. 12, 715393 (2021).","journal-title":"Front. Immunol."},{"key":"1305_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00725-8","volume":"8","author":"O Rossi","year":"2023","unstructured":"Rossi, O. et al. A next-generation GMMA-based vaccine candidate to fight shigellosis. NPJ vaccines 8, 130 (2023).","journal-title":"NPJ vaccines"},{"key":"1305_CR24","doi-asserted-by":"publisher","first-page":"e971","DOI":"10.1093\/infdis\/jiae273","volume":"230","author":"I Leroux-Roels","year":"2024","unstructured":"Leroux-Roels, I. et al. Safety and Immunogenicity of a 4-Component Generalized Modules for Membrane Antigens Shigella Vaccine in Healthy European Adults: Randomized, Phase 1\/2 Study. J. Infect. Dis. 230, e971\u2013e984 (2024).","journal-title":"J. Infect. Dis."},{"key":"1305_CR25","doi-asserted-by":"publisher","first-page":"e01020","DOI":"10.1128\/msphere.01020-21","volume":"7","author":"EA Odundo","year":"2022","unstructured":"Odundo, E. A. et al. Immunization of rabbits with a quadrivalent Shigella bioconjugate vaccine induces functional antibodies reactive with Shigella isolates from Kenya. Msphere 7, e01020\u2013e01021 (2022).","journal-title":"Msphere"},{"key":"1305_CR26","doi-asserted-by":"publisher","first-page":"4990","DOI":"10.1016\/j.vaccine.2017.07.070","volume":"35","author":"N Farzam","year":"2017","unstructured":"Farzam, N. et al. Vaccination with Shigella flexneri 2a conjugate induces type 2a and cross-reactive type 6 antibodies in humans but not in mice. Vaccine 35, 4990\u20134996 (2017).","journal-title":"Vaccine"},{"key":"1305_CR27","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1128\/IAI.67.2.782-788.1999","volume":"67","author":"FR Noriega","year":"1999","unstructured":"Noriega, F. R. et al. Strategy for cross-protection among Shigella flexneri serotypes. Infect. Immun. 67, 782\u2013788 (1999).","journal-title":"Infect. Immun."},{"key":"1305_CR28","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1016\/0264-410X(96)00006-0","volume":"14","author":"LL Van De Verg","year":"1996","unstructured":"Van De Verg, L. L. et al. Cross-reactivity of Shigella flexneri serotype 2a O antigen antibodies following immunization or infection. Vaccine 14, 1062\u20131068 (1996).","journal-title":"Vaccine"},{"key":"1305_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-80421-y","volume":"11","author":"F Mancini","year":"2021","unstructured":"Mancini, F. et al. Dissecting the contribution of O-Antigen and proteins to the immunogenicity of Shigella sonnei generalized modules for membrane antigens (GMMA). Sci. Rep. 11, 906 (2021).","journal-title":"Sci. Rep."},{"key":"1305_CR30","doi-asserted-by":"publisher","first-page":"568","DOI":"10.3390\/pharmaceutics16040568","volume":"16","author":"F Mancini","year":"2024","unstructured":"Mancini, F. et al. Testing S. sonnei GMMA with and without Aluminium Salt-Based Adjuvants in Animal Models. Pharmaceutics 16, 568 (2024).","journal-title":"Pharmaceutics"},{"key":"1305_CR31","doi-asserted-by":"publisher","first-page":"2806","DOI":"10.1021\/acs.jpcb.0c01595","volume":"124","author":"J Hlozek","year":"2020","unstructured":"Hlozek, J., Ravenscroft, N. & Kuttel, M. M. Effects of glucosylation and O-acetylation on the conformation of Shigella flexneri serogroup 2 O-antigen vaccine targets. J. Phys. Chem. B 124, 2806\u20132814 (2020).","journal-title":"J. Phys. Chem. B"},{"key":"1305_CR32","doi-asserted-by":"publisher","first-page":"2360","DOI":"10.3390\/microorganisms9112360","volume":"9","author":"V Arato","year":"2021","unstructured":"Arato, V. et al. Impact of O-Acetylation on S. flexneri 1b and 2a O-Antigen Immunogenicity in Mice. Microorganisms 9, 2360 (2021).","journal-title":"Microorganisms"},{"key":"1305_CR33","doi-asserted-by":"publisher","first-page":"29","DOI":"10.3390\/biotech11030029","volume":"11","author":"F Mancini","year":"2022","unstructured":"Mancini, F., Micoli, F. & Rossi, O. Setup and characterization of a high-throughput luminescence-based serum bactericidal assay (L-SBA) to determine functionality of human sera against Shigella flexneri. Biotech 11, 29 (2022).","journal-title":"Biotech"},{"key":"1305_CR34","doi-asserted-by":"publisher","first-page":"e1004749","DOI":"10.1371\/journal.ppat.1004749","volume":"11","author":"M Caboni","year":"2015","unstructured":"Caboni, M. et al. An O antigen capsule modulates bacterial pathogenesis in Shigella sonnei. PLoS Pathog. 11, e1004749 (2015).","journal-title":"PLoS Pathog."},{"key":"1305_CR35","doi-asserted-by":"crossref","unstructured":"Micoli, F., Alfini, R. & Giannelli, C. Methods for Assessment of OMV\/GMMA Quality and Stability. In: Bidmos, F., Boss\u00e9, J. & Langford, P. (eds). Bacterial Vaccines: Methods and Protocols. Springer US: New York, NY, 2022, 227-279.","DOI":"10.1007\/978-1-0716-1900-1_14"},{"key":"1305_CR36","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.jim.2018.06.025","volume":"461","author":"F Necchi","year":"2018","unstructured":"Necchi, F., Saul, A. & Rondini, S. Setup of luminescence-based serum bactericidal assay against Salmonella Paratyphi A. J. Immunological Methods 461, 117\u2013121 (2018).","journal-title":"J. Immunological Methods"},{"key":"1305_CR37","doi-asserted-by":"crossref","unstructured":"Mancini, F., Micoli, F. & Rossi, O. Setup and Characterization of a High-Throughput Luminescence-Based Serum Bactericidal Assay (L-SBA) to Determine Functionality of Human Sera against Shigella flexneri. BioTech (Basel) 11 (2022).","DOI":"10.3390\/biotech11030029"},{"key":"1305_CR38","doi-asserted-by":"publisher","first-page":"11123","DOI":"10.3390\/ijms252011123","volume":"25","author":"V Caradonna","year":"2024","unstructured":"Caradonna, V. et al. High-Throughput Luminescence-Based Serum Bactericidal Assay Optimization and Characterization to Assess Human Sera Functionality Against Multiple Shigella flexneri Serotypes. Int. J. Mol. Sci. 25, 11123 (2024).","journal-title":"Int. J. Mol. Sci."},{"key":"1305_CR39","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/ht9020014","volume":"9","author":"O Rossi","year":"2020","unstructured":"Rossi, O. et al. Intra-laboratory evaluation of luminescence based high-throughput serum bactericidal assay (L-SBA) to determine bactericidal activity of human sera against Shigella. High.-throughput 9, 14 (2020).","journal-title":"High.-throughput"}],"container-title":["npj Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41541-025-01305-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-025-01305-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-025-01305-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T12:02:38Z","timestamp":1766577758000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41541-025-01305-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,13]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1305"],"URL":"https:\/\/doi.org\/10.1038\/s41541-025-01305-8","relation":{},"ISSN":["2059-0105"],"issn-type":[{"value":"2059-0105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,13]]},"assertion":[{"value":"23 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"V. Caradonna is a student at the University of Siena and participates in a post-graduate studentship program at GSK. Usman Nakakana was a Senior Project Physician in GSK at the time of the study. All other authors are currently employed by the GSK group of companies. The authors declare no other financial or non-financial competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"266"}}