scholarly journals Mesenchymal Stem Cells Can both Enhance and Inhibit the Cellular Response to DNA Immunization by Genes of Nonstructural Proteins of the Hepatitis C Virus

2021 ◽  
Vol 22 (15) ◽  
pp. 8121
Author(s):  
Olga V. Masalova ◽  
Ekaterina I. Lesnova ◽  
Regina R. Klimova ◽  
Alexander V. Ivanov ◽  
Alla A. Kushch
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cellular Response ◽  
Cell Immune Response ◽  
Dna Immunization ◽  
Immunostimulatory Activity ◽  
Group 5 ◽  
Group 2 ◽  
High Level

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.

Neutralizing antibodies and broad, functional T cell immune response following immunization with hepatitis C virus proteins-based vaccine formulation

Vaccine ◽  
2014 ◽  
Vol 32 (15) ◽  
pp. 1720-1726 ◽  
Author(s):  
Gillian Martinez-Donato ◽  
Yalena Amador-Cañizares ◽  
Liz Alvarez-Lajonchere ◽  
Ivis Guerra ◽  
Angel Pérez ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Neutralizing Antibodies ◽  
Cell Immune Response ◽  
Vaccine Formulation ◽  
Hepatitis C Virus Proteins ◽  
Virus Proteins

scholarly journals Innate Immune Response against Hepatitis C Virus: Targets for Vaccine Adjuvants

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 313
Author(s):  
Daniel Sepulveda-Crespo ◽  
Salvador Resino ◽  
Isidoro Martinez
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Innate Immune Response ◽  
Vaccine Development ◽  
Innate Immune ◽  
World Health ◽  
Cell Immune Response ◽  
Vaccine Adjuvants

Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines. Recent studies on HCV-vaccine adjuvants have shown that the induction of a strong T- and B-cell immune response might be enhanced by choosing the right adjuvant.

A truncated variant of the hepatitis C virus core induces a slow but potent immune response in mice following DNA immunization

Vaccine ◽  
2000 ◽  
Vol 19 (7-8) ◽  
pp. 992-997 ◽  
Author(s):  
Santiago Dueñas-Carrera ◽  
Liz Alvarez-Lajonchere ◽  
Julio C. Alvarez-Obregón ◽  
Antonieta Herrera ◽  
Lázaro J. Lorenzo ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Dna Immunization ◽  
Virus Core ◽  
Potent Immune Response

DNA immunization with a plasmid carrying the gene of hepatitis C virus protein 5A (NS5A) induces an effective cellular immune response

2010 ◽  
Vol 44 (2) ◽  
pp. 245-253 ◽  
Author(s):  
O. V. Masalova ◽  
E. I. Lesnova ◽  
V. V. Grabovetskii ◽  
O. A. Smirnova ◽  
T. I. Ulanova ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cellular Immune Response ◽  
Virus Protein ◽  
Dna Immunization ◽  
Cellular Immune

scholarly journals Genetic Immunization of Wild-Type and Hepatitis C Virus Transgenic Mice Reveals a Hierarchy of Cellular Immune Response and Tolerance Induction against Hepatitis C Virus Structural Proteins

2001 ◽  
Vol 75 (24) ◽  
pp. 12121-12127 ◽  
Author(s):  
Jujin Satoi ◽  
Kazumoto Murata ◽  
Martin Lechmann ◽  
Elanchezhiyan Manickan ◽  
Zhensheng Zhang ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Transgenic Mice ◽  
Structural Proteins ◽  
Dna Immunization ◽  
Wild Type ◽  
Genetic Immunization ◽  
Cellular Immune ◽  
Hcv Structural Proteins

ABSTRACT To study the effect of genetic immunization on transgenic expression of hepatitis C virus (HCV) proteins, we evaluated the immunological response of HCV transgenic mice to HCV expression plasmids. FVB/n transgenic mice expressing HCV structural proteins (core, E1, and E2) and wild-type (WT) FVB/n mice were immunized intramuscularly with plasmids expressing core (pHCVcore) or core/E1/E2 (pHCVSt). After immunization, HCV-specific humoral and cellular immune response was studied. Both WT and transgenic mice immunized with either HCV construct produced antibodies and exhibited T-cell proliferative responses against core or envelope. In WT mice immunized with pHCVSt, cytotoxic T-lymphocyte (CTL) activities were detected against E2 but not against core or E1, whereas strong CTL activities against core could be detected in WT mice immunized with pHCVcore. In pHCVSt-immunized, transgenic mice, CTL activities against the core or envelope were completely absent, but core-specific CTL activities could be detected in pHCVcore-immunized transgenic mice. A similar pattern of immune responses was also observed in other mouse strains, including a transgenic line expressing human HLA-A2.1 molecules (AAD mice). Despite the presence of a peripheral cellular immunity against HCV, no liver pathology or lymphocytic infiltrate was observed in these transgenic mice. Our study suggests a hierarchy of CTL response against the HCV structural proteins (E2 > core > E1) in vivo when the proteins are expressed as a polyprotein. The HCV transgenic mice can be induced by DNA immunization to generate anti-HCV antibodies and anticore CTLs. However, they are tolerant at the CTL level against the E2 protein despite DNA immunization.

IV. Pathogenetic mechanisms involved in hepatitis C virus-induced liver diseases

1998 ◽  
Vol 275 (6) ◽  
pp. G1217-G1220 ◽  
Author(s):  
Johnson Yiu-Nam Lau
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Liver Damage ◽  
Cellular Response ◽  
High Dose ◽  
Acute Hepatitis C ◽  
Pathogenetic Mechanisms ◽  
Transplant Patients ◽  
Hepatocellular Damage ◽  
High Level

The pathogenetic mechanisms for liver damage in acute hepatitis C are not clear, but a host immune cellular response may be involved. In chronic hepatitis C, there is strong evidence that host cellular immune response is involved in the control of viral replication and contributes to hepatocellular damage. As hepatitis C virus infection persists, continuous liver damage and regeneration, together with enhanced fibrogenesis, may eventually lead to cirrhosis in a proportion of patients. Transplant patients on high-dose immunosuppression may have high-level intrahepatic hepatitis C viral expression, and, in this setting, the virus may induce direct cytopathic liver damage.

scholarly journals Hepatitis C Virus Adaptation to T-Cell Immune Pressure

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
A. Plauzolles ◽  
M. Lucas ◽  
S. Gaudieri
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Host Factors ◽  
Cell Immune Response ◽  
Viral Diversity ◽  
Immune Pressure ◽  
Viral Adaptation ◽  
Virus Adaptation

Replication of the hepatitis C virus (HCV) is an error-prone process. This high error rate results in the emergence of viral populations (quasispecies) within hosts and contributes to interhost variability. Numerous studies have demonstrated that both viral and host factors contribute to this viral diversity, which can ultimately affect disease outcome. As the host’s immune response is an important correlate of infection outcome for HCV, many of these viral variations are strongly influenced by T-cell immune pressure and accordingly constitute an efficient strategy to subvert such pressures (viral adaptations). This paper will review the data on viral diversity observed between and within hosts infected with HCV from the acute to the chronic stage of infection and will focus on viral adaptation to the host’s T-cell immune response.

scholarly journals Enhancing B- and T-Cell Immune Response to a Hepatitis C Virus E2 DNA Vaccine by Intramuscular Electrical Gene Transfer

2000 ◽  
Vol 74 (24) ◽  
pp. 11598-11607 ◽  
Author(s):  
Silvia Zucchelli ◽  
Stefania Capone ◽  
Elena Fattori ◽  
Antonella Folgori ◽  
Annalise Di Marco ◽  
...  
Keyword(s):  
T Cells ◽  
Electrical Stimulation ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Gene Transfer ◽  
Cellular Response ◽  
Low Voltage ◽  
Mouse Tissue ◽  
Cell Immune Response ◽  
Electric Pulses

ABSTRACT We describe an improved genetic immunization strategy for eliciting a full spectrum of anti-hepatitis C virus (HCV) envelope 2 (E2) glycoprotein responses in mammals through electrical gene transfer (EGT) of plasmid DNA into muscle fibers. Intramuscular injection of a plasmid encoding a cross-reactive hypervariable region 1 (HVR1) peptide mimic fused at the N terminus of the E2 ectodomain, followed by electrical stimulation treatment in the form of high-frequency, low-voltage electric pulses, induced more than 10-fold-higher expression levels in the transfected mouse tissue. As a result of this substantial increment of in vivo antigen production, the humoral response induced in mice, rats, and rabbits ranged from 10- to 30-fold higher than that induced by conventional naked DNA immunization. Consequently, immune sera from EGT-treated mice displayed a broader cross-reactivity against HVR1 variants from natural isolates than sera from injected animals that were not subjected to electrical stimulation. Cellular response against E2 epitopes specific for helper and cytotoxic T cells was significantly improved by EGT. The EGT-mediated enhancement of humoral and cellular immunity is antigen independent, since comparable increases in antibody response against ciliary neurotrophic factor or in specific anti-human immunodeficiency virus type 1 gag CD8+ T cells were obtained in rats and mice. Thus, the method described potentially provides a safe, low-cost treatment that may be scaled up to humans and may hold the key for future development of prophylactic or therapeutic vaccines against HCV and other infectious diseases.

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