Masalova O V, Lesnova E I, Andreev S M, Shershakova N N, Kozlov V V, Permyakova K Y, Demidova N A, Valuev-Elliston V T, Turetskiy E A, Ivanov A V, Nikolaeva T N, Khaitov M R, Pronin A V, Kushch A A
Gamaleya NRC of Epidemiology and Microbiology, Ministry of Health of the Russian Federation.
NRC Institute of Immunology FMBA of Russia.
Vopr Virusol. 2023 Feb 7;67(6):516-526. doi: 10.36233/0507-4088-149.
A vaccine against hepatitis C has not yet been developed. Recombinant proteins and plasmids encoding hepatitis C virus (HCV) proteins, the components of candidate vaccines, induce a weak immune response and require the use of adjuvants. The aim of the work was to study the adjuvant action of an aqueous solution of fullerene C60 during immunization of mice with HCV recombinant protein NS5B (rNS5B) that is an RNA-dependent RNA polymerase, or with NS5B-encoding pcNS5B plasmid.
An aqueous solution of dispersed fullerene (dnC60) was obtained by ultrafiltration. C57BL/6 mice were immunized with rNS5B subcutaneously, pcNS5B intramuscularly mixed with different doses of dnC60 three times, then the humoral and cellular response to HCV was evaluated.
Mice immunization with rNS5B in a mixture with dnC60 at doses of 250 g/mouse significantly induced humoral response: a dose-dependent increase in IgG1 antibody titers was 720 times higher than in the absence of fullerene. There was no increase in the cellular response to rNS5B when administered with dnC60. The humoral response to DNA immunization was weak in mice of all groups receiving pcNS5B. The cellular response was suppressed when the plasmid was injected in a mixture with dnC60.
Dispersed fullerene dnC60 is a promising adjuvant for increasing the immunostimulating activity of weakly immunogenic proteins including surface and other HCV proteins, important for a protective response. Further research is needed to enhance the ability of dnC60 to boost the cellular immune response to the components of the candidate vaccine.
丙型肝炎疫苗尚未研发出来。编码丙型肝炎病毒（HCV）蛋白的重组蛋白和质粒作为候选疫苗的成分，诱导的免疫反应较弱，需要使用佐剂。这项工作的目的是研究富勒烯C60水溶液在小鼠用HCV重组蛋白NS5B（rNS5B，一种依赖RNA的RNA聚合酶）或编码NS5B的pcNS5B质粒免疫过程中的佐剂作用。
通过超滤获得分散富勒烯（dnC60）水溶液。将C57BL/6小鼠皮下注射rNS5B，将pcNS5B与不同剂量的dnC60肌肉内混合注射三次，然后评估对HCV的体液和细胞反应。
用250μg/小鼠剂量的dnC60与rNS5B混合免疫小鼠显著诱导了体液反应：IgG1抗体滴度呈剂量依赖性增加，比不使用富勒烯时高720倍。与dnC60一起给药时，对rNS5B的细胞反应没有增加。在所有接受pcNS5B的小鼠组中，DNA免疫的体液反应较弱。当质粒与dnC60混合注射时，细胞反应受到抑制。
分散富勒烯dnC60是一种有前景的佐剂，可提高包括表面蛋白和其他HCV蛋白在内的弱免疫原性蛋白的免疫刺激活性，这对保护性反应很重要。需要进一步研究以增强dnC60增强对候选疫苗成分的细胞免疫反应的能力。
