Human Mesenchymal Stem Cells Modified with the NS5A Gene of Hepatitis C Virus Induce a Cellular Immune Response Exceeding the Response to DNA Immunization with This Gene
Olga V. Masalova,
Ekaterina I. Lesnova,
Vladimir A. Kalsin,
Regina R. Klimova,
Natalya E. Fedorova,
Vyacheslav V. Kozlov,
Natalya A. Demidova,
Kirill I. Yurlov,
Mikhail A. Konoplyannikov,
Tatyana N. Nikolaeva,
Alexander V. Pronin,
Vladimir P. Baklaushev,
Alla A. Kushch
Affiliations
Olga V. Masalova
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Ekaterina I. Lesnova
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Vladimir A. Kalsin
Federal Research Clinical Center of Specialized Medical Care and Medical Technologies, Federal Medical-Biological Agency of the Russian Federation, 115682 Moscow, Russia
Regina R. Klimova
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Natalya E. Fedorova
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Vyacheslav V. Kozlov
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Natalya A. Demidova
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Kirill I. Yurlov
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Mikhail A. Konoplyannikov
Federal Research Clinical Center of Specialized Medical Care and Medical Technologies, Federal Medical-Biological Agency of the Russian Federation, 115682 Moscow, Russia
Tatyana N. Nikolaeva
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Alexander V. Pronin
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Vladimir P. Baklaushev
Federal Research Clinical Center of Specialized Medical Care and Medical Technologies, Federal Medical-Biological Agency of the Russian Federation, 115682 Moscow, Russia
Alla A. Kushch
Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Hepatitis C virus (HCV) is one of the basic culprits behind chronic liver disease, which may result in cirrhosis and hepatocarcinoma. In spite of the extensive research conducted, a vaccine against HCV has not been yet created. We have obtained human mesenchymal stem cells (hMSCs) and used them for expressing the HCV NS5A protein as a model vaccination platform. Sixteen hMSC lines of a different origin were transfected with the pcNS5A-GFP plasmid to obtain genetically modified MSCs (mMSCs). The highest efficiency was obtained by the transfection of dental pulp MSCs. C57BL/6 mice were immunized intravenously with mMSCs, and the immune response was compared with the response to the pcNS5A-GFP plasmid, which was injected intramuscularly. It was shown that the antigen-specific lymphocyte proliferation and the number of IFN-γ-synthesizing cells were two to three times higher after the mMSC immunization compared to the DNA immunization. In addition, mMSCs induced more CD4+ memory T cells and an increase in the CD4+/CD8+ ratio. The results suggest that the immunostimulatory effect of mMSCs is associated with the switch of MSCs to the pro-inflammatory phenotype and a decrease in the proportion of myeloid derived suppressor cells. Thus, the possibility of using human mMSCs for the creation of a vaccine against HCV has been shown for the first time.
