{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T20:06:00Z","timestamp":1784664360522,"version":"3.55.0"},"reference-count":72,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T00:00:00Z","timestamp":1624665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-74-10086"],"award-info":[{"award-number":["19-74-10086"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hepatitis C virus (HCV) is one of the main triggers of chronic liver disease. Despite tremendous progress in the HCV field, there is still no vaccine against this virus. Potential vaccines can be based on its recombinant proteins. To increase the humoral and, especially, cellular immune response to them, more effective adjuvants are needed. Here, we evaluated a panel of compounds as potential adjuvants using the HCV NS5B protein as an immunogen. These compounds included inhibitors of polyamine biosynthesis and urea cycle, the mTOR pathway, antioxidants, and cellular receptors. A pronounced stimulation of cell proliferation and interferon-\u03b3 (IFN-\u03b3) secretion in response to concanavalin A was shown for antioxidant N-acetylcysteine (NAC), polyamine biosynthesis inhibitor 2-difluoromethylornithine (DFMO), and TLR9 agonist CpG ODN 1826 (CpG). Their usage during the immunization of mice with the recombinant NS5B protein significantly increased antibody titers, enhanced lymphocyte proliferation and IFN-\u03b3 production. NAC and CpG decreased relative Treg numbers; CpG increased the number of myeloid-derived suppressor cells (MDSCs), whereas neither NAC nor DFMO affected MDSC counts. NAC and DFMO suppressed NO and interleukin 10 (IL-10) production by splenocytes, while DFMO increased the levels of IL-12. This is the first evidence of immunomodulatory activity of NAC and DFMO during prophylactic immunization against infectious diseases.<\/jats:p>","DOI":"10.3390\/ijms22136892","type":"journal-article","created":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T22:24:57Z","timestamp":1624832697000},"page":"6892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Difluoromethylornithine (DFMO), an Inhibitor of Polyamine Biosynthesis, and Antioxidant N-Acetylcysteine Potentiate Immune Response in Mice to the Recombinant Hepatitis C Virus NS5B Protein"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2801-6843","authenticated-orcid":false,"given":"Ekaterina I.","family":"Lesnova","sequence":"first","affiliation":[{"name":"Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5571-5669","authenticated-orcid":false,"given":"Olga V.","family":"Masalova","sequence":"additional","affiliation":[{"name":"Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3579-4416","authenticated-orcid":false,"given":"Kristina Yu.","family":"Permyakova","sequence":"additional","affiliation":[{"name":"Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia"},{"name":"Federal State Budgetary Educational Institution of Higher Education \u201cMoscow State Academy of Veterinary Medicine and Biotechnology\u2014MVA by K.I. Skryabin\u201d, 109472 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyacheslav V.","family":"Kozlov","sequence":"additional","affiliation":[{"name":"Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana N.","family":"Nikolaeva","sequence":"additional","affiliation":[{"name":"Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5266-9783","authenticated-orcid":false,"given":"Alexander V.","family":"Pronin","sequence":"additional","affiliation":[{"name":"Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3396-5533","authenticated-orcid":false,"given":"Vladimir T.","family":"Valuev-Elliston","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5659-9679","authenticated-orcid":false,"given":"Alexander V.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alla A.","family":"Kushch","sequence":"additional","affiliation":[{"name":"Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.immuni.2013.12.010","article-title":"Immune responses to HCV and other Hepatitis viruses","volume":"40","author":"Park","year":"2014","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"826","DOI":"10.2174\/1389450116666150825110532","article-title":"Innate and adaptive immune responses in chronic HCV infection","volume":"18","author":"Dustin","year":"2017","journal-title":"Curr. 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