Genetically Modified Mouse Mesenchymal Stem Cells Expressing Non-Structural Proteins of Hepatitis C Virus Induce Effective Immune Response
Olga V. Masalova,
Ekaterina I. Lesnova,
Regina R. Klimova,
Ekaterina D. Momotyuk,
Vyacheslav V. Kozlov,
Alla M. Ivanova,
Olga V. Payushina,
Nina N. Butorina,
Natalia F. Zakirova,
Alexander N. Narovlyansky,
Alexander V. Pronin,
Alexander V. Ivanov,
Alla A. Kushch
Affiliations
Olga V. Masalova
Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, Russia
Ekaterina I. Lesnova
Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, Russia
Regina R. Klimova
Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, Russia
Ekaterina D. Momotyuk
Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, Russia
Vyacheslav V. Kozlov
Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, Russia
Alla M. Ivanova
Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, Russia
Olga V. Payushina
Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow 119991, Russia
Nina N. Butorina
Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Moscow 119334, Russia
Natalia F. Zakirova
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
Alexander N. Narovlyansky
Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, Russia
Alexander V. Pronin
Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, Russia
Alexander V. Ivanov
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia
Alla A. Kushch
Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, Russia
Hepatitis C virus (HCV) is one of the major causes of chronic liver disease and leads to cirrhosis and hepatocarcinoma. Despite extensive research, there is still no vaccine against HCV. In order to induce an immune response in DBA/2J mice against HCV, we obtained modified mouse mesenchymal stem cells (mMSCs) simultaneously expressing five nonstructural HCV proteins (NS3-NS5B). The innate immune response to mMSCs was higher than to DNA immunization, with plasmid encoding the same proteins, and to naïve unmodified MSCs. mMSCs triggered strong phagocytic activity, enhanced lymphocyte proliferation, and production of type I and II interferons. The adaptive immune response to mMSCs was also more pronounced than in the case of DNA immunization, as exemplified by a fourfold stronger stimulation of lymphocyte proliferation in response to HCV, a 2.6-fold higher rate of biosynthesis, and a 30-fold higher rate of secretion of IFN-γ, as well as by a 40-fold stronger production of IgG2a antibodies to viral proteins. The immunostimulatory effect of mMSCs was associated with pronounced IL-6 secretion and reduction in the population of myeloid derived suppressor cells (MDSCs). Thus, this is the first example that suggests the feasibility of using mMSCs for the development of an effective anti-HCV vaccine.
