Abstract
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-γ (IFN-γ) 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-γ 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.
Highlights
Hepatitis C virus (HCV) is one of the leading causes of chronic liver diseases including its end-stage pathologies—cirrhosis and hepatocellular carcinoma
Analysis of splenocyte receptors after administration of emulsion CpG ODN 1826 in an incomplete Freund’s adjuvant (IFA) revealed that the relative number of CD4+ and CD8+ T cells decreased by 1.2–1.4-fold (p < 0.05)
Development of effective and safe vaccines against hepatitis C requires a search for novel adjuvants with high protective activity lacking the drawback of the currently used analogs
Summary
Hepatitis C virus (HCV) is one of the leading causes of chronic liver diseases including its end-stage pathologies—cirrhosis and hepatocellular carcinoma. As a result of development of direct-acting antivirals (DAAs) and their introduction into clinical practice in early 2010s, CHC has become curable for more than 90% of the patients. Eradication of the disease is still hampered by several factors. Such DAAs are not widely accessible for patients, as their price in many countries remains very high. DAAs do not reduce risks of virus-associated end-stage liver diseases to the level of the general population [7]. Attempts to develop prophylactic and therapeutic vaccines against hepatitis C that were paused upon bringing the first DAAs to the market have again been intensified in recent years. The lack of a vaccine can be one of the major obstacles to hepatitis C control [8]
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