{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:13:51Z","timestamp":1787030031792,"version":"build-2736575974"},"reference-count":95,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Gates Foundation","doi-asserted-by":"publisher","award":["INV-037306"],"award-info":[{"award-number":["INV-037306"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Shigella is the leading bacterial cause of diarrheal disease worldwide. Although multiple vaccine candidates are under development and in clinical trials, no Shigella vaccine is currently available on the market. Shigella comprises four species: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei. S. flexneri has been recognized as the most prevalent species, particularly in low- and middle-income countries (LMICs), and the top serotypes are S. flexneri 2a, 3a and 6. Conversely, S. sonnei has a single serotype and predominates in high-income countries (HICs). Invasion plasmid antigen B (IpaB) is a critical virulence factor of Shigella type III secretion system (T3SS) that is highly conserved across Shigella serotypes. Here, we report the development of a Shigella quadrivalent O-polysaccharide-IpaB conjugate vaccine candidate (IVT Shigella-04). Methods: IVT Shigella-04 contains O-polysaccharides (O-PS) from S. flexneri 2a, 3a, 6, and S. sonnei, each individually conjugated to recombinantly expressed IpaB as the carrier protein using 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) chemistry. The immunogenicity of IVT Shigella-04 was evaluated in a rabbit immunization model. Results: Baseline (day 0) IgG concentrations were low for all four Shigella serotypes (&lt;0.5 \u00b5g\/mL). Following two doses on day 0 and day 28 (2.5 \u00b5g of each conjugate per dose; total 10 \u00b5g), IgG geometric mean concentrations increased significantly (p &lt; 0.001) by day 42, reaching 67.96 \u00b5g\/mL (2a), 91.56 \u00b5g\/mL (3a), 371.31 \u00b5g\/mL (6), and 11.00 \u00b5g\/mL (sonnei). Consistently, serum bactericidal activity (SBA) at day 42 increased 13-fold (2a), 34-fold (3a), 63-fold (6), and 224-fold (sonnei) relative to baseline (day 0). Conclusions: IVT Shigella-04 elicited robust serotype-specific humoral and functional immune responses in preclinical models, supporting its further development toward clinical evaluation.<\/jats:p>","DOI":"10.3390\/vaccines14020134","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:04:46Z","timestamp":1769612686000},"page":"134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development of a Novel Shigella Quadrivalent Conjugate Vaccine Using Shigella O-Polysaccharide and IpaB Carrier Protein"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-555X","authenticated-orcid":false,"given":"Shangdong","family":"Guo","sequence":"first","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2357-8356","authenticated-orcid":false,"given":"Richa","family":"Puri","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3054-0018","authenticated-orcid":false,"given":"Harshita","family":"Seth","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neza","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gowri","family":"Chellappan","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Seal","sequence":"additional","affiliation":[{"name":"Immunology, Manufacturing Sciences and Technology, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6066-3357","authenticated-orcid":false,"given":"Yutai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Immunology, Manufacturing Sciences and Technology, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9307-5310","authenticated-orcid":false,"given":"Giriraj","family":"Chalke","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aakriti","family":"Bajracharya","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Wright","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winston Umakanth","family":"Balasundaram","sequence":"additional","affiliation":[{"name":"Quality Control\/Micro, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Ghayal","sequence":"additional","affiliation":[{"name":"Quality Control\/Micro, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimple","family":"Machado","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen","family":"Gan","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geetha","family":"Karengil","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gowthami Jagruthi","family":"Penumaka","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Shay","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chathuranga","family":"Siriwardhana","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3796-6891","authenticated-orcid":false,"given":"Anup","family":"Datta","sequence":"additional","affiliation":[{"name":"Bacterial Research and Development, Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6642-1128","authenticated-orcid":false,"given":"Subhash V.","family":"Kapre","sequence":"additional","affiliation":[{"name":"Inventprise, Inc., Redmond, WA 98052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lubeck-Schricker, M., Rivas-Nieto, A.C., Rosauer, J., Mpinganjira, S., Malhotra, A., Bastias, M., Rogawski McQuade, E., Kosek, M., Lanata, C.F., and Paredes Olortegui, M. 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