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Genetically Modified Mouse Mesenchymal Stem Cells Expressing Non-Structural Proteins of Hepatitis C Virus Induce Effective Immune Response.

ABSTRACT: 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-?, 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.

SUBMITTER: Masalova OV

PROVIDER: S-EPMC7158691 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Genetically Modified Mouse Mesenchymal Stem Cells Expressing Non-Structural Proteins of Hepatitis C Virus Induce Effective Immune Response.

Masalova Olga V OV Lesnova Ekaterina I EI Klimova Regina R RR Momotyuk Ekaterina D ED Kozlov Vyacheslav V VV Ivanova Alla M AM Payushina Olga V OV Butorina Nina N NN Zakirova Natalia F NF Narovlyansky Alexander N AN Pronin Alexander V AV Ivanov Alexander V AV Kushch Alla A AA

Vaccines 20200202 1

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 t ...[more]

PMID: 32024236

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Project description:BackgroundMalaria is one of the most lethal infectious diseases in tropical and subtropical areas of the world. Paratransgenesis using symbiotic bacteria offers a sustainable and environmentally friendly strategy to combat this disease. In the study reported here, we evaluated the disruption of malaria transmission in the Anopheles stephensi-Plasmodium berghei assemblage using the wild-type (WT) and three modified strains of the insect gut bacterium, Enterobacter cloacae.MethodsThe assay was carried out using the E. cloacae dissolvens WT and three engineered strains (expressing green fluorescent protein-defensin (GFP-D), scorpine-HasA (S-HasA) and HasA only, respectively). Cotton wool soaked in a solution of 5% (wt/vol) fructose + red dye (1/50 ml) laced with one of the bacterial strains (1 × 109cells/ml) was placed overnight in cages containing female An. stephensi mosquitoes (age: 3-5 days). Each group of sugar-fed mosquitoes was then starved for 4-6 h, following which time they were allowed to blood-feed on P. berghei-infected mice for 20 min in the dark at 17-20 °C. The blood-fed mosquitoes were kept at 19 ± 1 °C and 80 ± 5% relative humidity, and parasite infection was measured by midgut dissection and oocyst counting 10 days post-infection (dpi).ResultsExposure to both WT and genetically modified E. cloacae dissolvens strains significantly (P < 0.0001) disrupted P. berghei development in the midgut of An. stephensi, in comparison with the control group. The mean parasite inhibition of E. cloacaeWT, E. cloacaeHasA, E. cloacaeS-HasA and E. cloacaeGFP-D was measured as 72, 86, 92.5 and 92.8 respectively.ConclusionsThe WT and modified strains of E. cloacae have the potential to abolish oocyst development by providing a physical barrier or through the excretion of intrinsic effector molecules. These findings reinforce the case for the use of either WT or genetically modified strains of E. cloacae bacteria as a powerful tool to combat malaria.

Dataset Information

Genetically Modified Mouse Mesenchymal Stem Cells Expressing Non-Structural Proteins of Hepatitis C Virus Induce Effective Immune Response.

Publications

Genetically Modified Mouse Mesenchymal Stem Cells Expressing Non-Structural Proteins of Hepatitis C Virus Induce Effective Immune Response.

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