Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Int J Mol Sci. 2021 Jul 29;22(15):8121. doi: 10.3390/ijms22158121.
Despite extensive research, there is still no vaccine against the hepatitis C virus (HCV). The aim of this study was to investigate whether MSCs can exhibit adjuvant properties during DNA vaccination against hepatitis C. We used the pcNS3-NS5B plasmid encoding five nonstructural HCV proteins and MSCs derived from mice bone marrow. Five groups of DBA mice were immunized with the plasmid and/or MSCs in a different order. Group 1 was injected with the plasmid twice at intervals of 3 weeks; Group 2 with the plasmid, and after 24 h with MSCs; Group 3 with MSCs followed by the plasmid the next day; Group 4 with only MSCs; and Group 5 with saline. When the MSCs were injected prior to DNA immunization, the cell immune response to HCV proteins assessed by the level of IFN-γ synthesis was markedly increased compared to DNA alone. In contrast, MSCs injected after DNA suppressed the immune response. Apparently, the high level of proinflammatory cytokines detected after DNA injection promotes the conversion of MSCs introduced later into the immunosuppressive MSC2. The low level of cytokines in mice before MSC administration promotes the high immunostimulatory activity of MSC1 in response to a DNA vaccine. Thus, when administered before DNA, MSCs are capable of exhibiting promising adjuvant properties.
尽管进行了广泛的研究，但目前仍没有针对丙型肝炎病毒 (HCV) 的疫苗。本研究旨在探讨间充质干细胞 (MSC) 在丙型肝炎 DNA 疫苗接种中是否具有佐剂特性。我们使用 pcNS3-NS5B 质粒编码五个非结构 HCV 蛋白和来自小鼠骨髓的 MSC。五组 DBA 小鼠以不同的顺序用质粒和/或 MSC 进行免疫接种。第 1 组在间隔 3 周的时间内两次注射质粒；第 2 组注射质粒，并在 24 小时后注射 MSC；第 3 组先注射 MSC，第二天再注射质粒；第 4 组仅注射 MSC；第 5 组注射生理盐水。当 MSC 在 DNA 免疫接种之前注射时，通过 IFN-γ 合成水平评估对 HCV 蛋白的细胞免疫反应明显增加，与单独 DNA 相比。相反，注射 DNA 后 MSC 会抑制免疫反应。显然，DNA 注射后检测到的高水平促炎细胞因子促进了随后引入的 MSC 向具有免疫抑制作用的 MSC2 的转化。在 MSC 给药之前，小鼠中的细胞因子水平较低，可促进 MSC1 对 DNA 疫苗产生高免疫刺激活性。因此，当在 DNA 之前给药时，MSC 能够表现出有前途的佐剂特性。
