Investigation of the Immunomodulatory effect of Berberis vulgaris on core-pulsed dendritic cell vaccine.

Doaa A Ghareeb,Eiman H Elwakeel,Mina S Aziz,Maha A El Demellawy,Rowaida Khalil

doi:10.1186/s12906-016-1327-2

Abstract

BackgroundVirus-induced dendritic cells (DCs) functional deficiency leads to sub-optimal initiation of adaptive immune responses and consequently chronic infection establishment. The present study reports an advanced hepatitis C virus (HCV) therapeutic vaccine model based on In vivo enrichment of DCs with barberry ethanolic crude extract (BCE) then pulsing them with HCV core protein.MethodsDCs were enriched by BCE intravenous injection in BALB/c mice. Vaccine efficiency was assessed by flow cytometric analysis of splenocytes of immunized mice, cytokine profiling, cytotoxic T lymphocyte assay, and humoral immune response assessment.ResultsThere was no significant difference in surface phenotypic characterization of splenocytes from mice immunized with non-BCE-enriched-core-pulsed DCs (iDcs-core) compared to those from mice injected with RPMI-1640 medium. However, splenocytes from mice immunized with BCE-enriched-core-pulsed DCs showed 197 % increase in CD16+ population, 33 % increase in MHCII+ population, and 43 % decrease in CD3+ population. In iDCs-core group, 57.9 % greater anti-core cytotoxic T lymphocyte activity, up-regulation in interferon gamma and interleukin (IL) -12 expression, and down-regulation in IL-4 and IL-10 were recorded. Moreover, sustained specific anti-core antibodies were detected only in sera of the same group.Conclusionsresults indicate that BCE-enriched-core-transduced DCs may serve as a new model for immunotherapy of HCV chronic infection.

Highlights

Virus-induced dendritic cells (DCs) functional deficiency leads to sub-optimal initiation of adaptive immune responses and chronic infection establishment
The present study reports an advanced hepatitis C virus (HCV) therapeutic vaccine model based on In-vivo enrichment of DCs with barberry ethanolic crude extract (BCE) and pulsing them with HCV core protein
The barberry extract powder form was kept at −20 °C until subjected to further biochemical analysis BALB/c female mice, inbred strain (8–10 weeks of age, 25–30 g body weight) were purchased from experimental animal house (Tudor Belharis Research Institute), and housed in the animal house of Medical Technology Centre, Medical Research Institute, Alexandria University, Egypt. all study protocols for animal and biological tissue samples treatment, involved in this study, were firmly subjected to ethical instructions outlined by Animal Ethics Committees (AEC) that published via The National Health and Medical Research Council (NHMRC) policies and guidelines that recommended by the Egyptian Ministry of Health and Population, High Committee Of Medical Specialties, Arab Republic of Egypt [16]

Summary

Introduction

Virus-induced dendritic cells (DCs) functional deficiency leads to sub-optimal initiation of adaptive immune responses and chronic infection establishment. Development of an effective vaccine against HCV infection has long been defined as a difficult challenge. This is due to the quasispecies nature of the virus due to the lack of proofreading activity of the viral RNAdependent RNA polymerase, and the observation that convalescent humans and chimpanzees could be reinfected upon re-exposure [5]. Virus-induced defect in DCs function is one of the mechanisms responsible for immune evasion of HCV. Vaccination strategies to induce strong anti-HCV T cell responses are essential for both of prophylactic and therapeutic purposes

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