{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T07:15:25Z","timestamp":1778397325563,"version":"3.51.4"},"reference-count":22,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"government","award":["14.N08.11.2009"],"award-info":[{"award-number":["14.N08.11.2009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>A multivalent vaccine is much needed to achieve protection against predominant Shigella serotypes. Recently, we demonstrated the clinical applicability and immunogenic potential of tri-acylated S. flexneri 2a lipopolysaccharide (Ac3-S-LPS). Using a similar approach, we designed a pentavalent LPS candidate vaccine against S. flexneri 1b, 2a, 3a, 6, and Y (PLVF). In this study, we performed molecular and antigenic characterization of the vaccine candidate and its preclinical evaluation. There were no signs of acute toxicity after subcutaneous administration of PLVF in rabbits at a proposed human dose of 125 \u03bcg. No pyrogenic reactions and adverse effects associated with chronic toxicity after repeated administration of PLVF were revealed either. The immunization of mice with PLVF led to \u226516-fold increase in S. flexneri 1b-, 2a-, 3a-, 6-, and Y-specific antibodies. In a serum bactericidal antibody (SBA) assay, we registered 54%, 66%, 35%, 60%, and 60% killing of S. flexneri 1b, 2a, 3a, 6, and Y, respectively. In the guinea pig keratoconjunctivitis model, the efficacy was 50% to 75% against challenge with all five S. flexneri serotypes. These studies demonstrate that PLVF is safe, immunogenic over a wide range of doses, and provides protection against challenge with homologous S. flexneri strains, thus confirming the validity of pentavalent design of the combined vaccine.<\/jats:p>","DOI":"10.3390\/vaccines11020345","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T02:35:10Z","timestamp":1675391710000},"page":"345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Pentavalent Shigella flexneri LPS-Based Vaccine Candidate Is Safe and Immunogenic in Animal Models"],"prefix":"10.3390","volume":"11","author":[{"given":"Vladimir A.","family":"Ledov","sequence":"first","affiliation":[{"name":"Laboratory of Carbohydrate Vaccines, National Research Center-Institute of Immunology, Federal Medical Biological Agency of Russia, 24, Kashirskoe Shosse, 115478 Moscow, Russia"},{"name":"ATVD-TEAM Co., Ltd., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina E.","family":"Golovina","sequence":"additional","affiliation":[{"name":"Laboratory of Carbohydrate Vaccines, National Research Center-Institute of Immunology, Federal Medical Biological Agency of Russia, 24, Kashirskoe Shosse, 115478 Moscow, Russia"},{"name":"ATVD-TEAM Co., Ltd., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biana I.","family":"Alkhazova","sequence":"additional","affiliation":[{"name":"ATVD-TEAM Co., Ltd., 115522 Moscow, Russia"},{"name":"Laboratory of Preparative Biochemistry, National Research Center-Institute of Immunology, Federal Medical Biological Agency of Russia, 24, Kashirskoe Shosse, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vyacheslav L.","family":"Lvov","sequence":"additional","affiliation":[{"name":"ATVD-TEAM Co., Ltd., 115522 Moscow, Russia"},{"name":"Laboratory of Preparative Biochemistry, National Research Center-Institute of Immunology, Federal Medical Biological Agency of Russia, 24, Kashirskoe Shosse, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander L.","family":"Kovalchuk","sequence":"additional","affiliation":[{"name":"Laboratory of Carbohydrate Vaccines, National Research Center-Institute of Immunology, Federal Medical Biological Agency of Russia, 24, Kashirskoe Shosse, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr G.","family":"Aparin","sequence":"additional","affiliation":[{"name":"Laboratory of Carbohydrate Vaccines, National Research Center-Institute of Immunology, Federal Medical Biological Agency of Russia, 24, Kashirskoe Shosse, 115478 Moscow, Russia"},{"name":"ATVD-TEAM Co., Ltd., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S0140-6736(17)33296-8","article-title":"Shigellosis","volume":"391","author":"Kotloff","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): A prospective, case-control study","volume":"382","author":"Kotloff","year":"2013","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4269\/ajtmh.2009.80.609","article-title":"Global etiology of travelers\u2019 diarrhea: Systematic review from 1973 to the present","volume":"80","author":"Shah","year":"2009","journal-title":"Am. 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