In vitro stimulation with HBV therapeutic vaccine candidate Nasvac activates B and T cells from chronic hepatitis B patients and healthy donors

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In vitro stimulation with HBV therapeutic vaccine candidate Nasvac activates B and T cells from chronic hepatitis B patients and healthy donors. / Lobaina, Yadira; Hardtke, Svenja; Wedemeyer, Heiner; Aguilar, Julio Cesar; Schlaphoff, Verena.

In: MOL IMMUNOL, Vol. 63, No. 2, 02.2015, p. 320-7.

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@article{b0cb854f33524414a883bdfd5b745d36,
title = "In vitro stimulation with HBV therapeutic vaccine candidate Nasvac activates B and T cells from chronic hepatitis B patients and healthy donors",
abstract = "Hepatitis B virus (HBV) chronic infections remain a considerable health problem worldwide. The standard therapies have demonstrated limited efficacy, side effects or need life-long treatments. Nowadays therapeutic vaccination is a promising option. Recently, we developed a new vaccine formulation called Nasvac, based on the combination of surface and core antigens from HBV. Clinical trials already performed showed good efficacy in virus control. However, the exact mode of action of Nasvac formulation remains unclear. So far the functional impairment of DCs during persistent HBV infection is a controversial issue. On the other hand, it is known that B cells may function as antigen presenting cells (APC) activating T cells. The hepatitis B core antigen contained in Nasvac vaccine is able to bind and activate a high frequency of naive human B cells. In the present study the surface expression of activation and exhaustion markers on B cells and the subsequent activation of T cells after in vitro stimulation with Nasvac antigens were evaluated in chronic HBV patients and healthy donors. B- and T-cell phenotype and proliferation were assessed by flow cytometry. Our results indicate that in contrast to exhaustions markers B cell activation markers were increased on both study groups after Nasvac stimulation. A shift toward an activation phenotype was observed for both B and T cells. The present work suggests that B cells could act as efficient APCs for Nasvac antigens in humans, which might suggest the use of activated B cells as immunotherapeutic strategy for chronic hepatitis B. ",
keywords = "B-Lymphocytes/cytology, Biomarkers/metabolism, Cell Proliferation, Female, Hepatitis B Vaccines/immunology, Hepatitis B virus/immunology, Hepatitis B, Chronic/immunology, Humans, Lymphocyte Activation/immunology, Male, T-Lymphocytes/cytology, Tissue Donors",
author = "Yadira Lobaina and Svenja Hardtke and Heiner Wedemeyer and Aguilar, {Julio Cesar} and Verena Schlaphoff",
note = "Copyright {\textcopyright} 2014 Elsevier Ltd. All rights reserved.",
year = "2015",
month = feb,
doi = "10.1016/j.molimm.2014.08.003",
language = "English",
volume = "63",
pages = "320--7",
journal = "MOL IMMUNOL",
issn = "0161-5890",
publisher = "Elsevier Limited",
number = "2",

}

RIS

TY - JOUR

T1 - In vitro stimulation with HBV therapeutic vaccine candidate Nasvac activates B and T cells from chronic hepatitis B patients and healthy donors

AU - Lobaina, Yadira

AU - Hardtke, Svenja

AU - Wedemeyer, Heiner

AU - Aguilar, Julio Cesar

AU - Schlaphoff, Verena

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2015/2

Y1 - 2015/2

N2 - Hepatitis B virus (HBV) chronic infections remain a considerable health problem worldwide. The standard therapies have demonstrated limited efficacy, side effects or need life-long treatments. Nowadays therapeutic vaccination is a promising option. Recently, we developed a new vaccine formulation called Nasvac, based on the combination of surface and core antigens from HBV. Clinical trials already performed showed good efficacy in virus control. However, the exact mode of action of Nasvac formulation remains unclear. So far the functional impairment of DCs during persistent HBV infection is a controversial issue. On the other hand, it is known that B cells may function as antigen presenting cells (APC) activating T cells. The hepatitis B core antigen contained in Nasvac vaccine is able to bind and activate a high frequency of naive human B cells. In the present study the surface expression of activation and exhaustion markers on B cells and the subsequent activation of T cells after in vitro stimulation with Nasvac antigens were evaluated in chronic HBV patients and healthy donors. B- and T-cell phenotype and proliferation were assessed by flow cytometry. Our results indicate that in contrast to exhaustions markers B cell activation markers were increased on both study groups after Nasvac stimulation. A shift toward an activation phenotype was observed for both B and T cells. The present work suggests that B cells could act as efficient APCs for Nasvac antigens in humans, which might suggest the use of activated B cells as immunotherapeutic strategy for chronic hepatitis B.

AB - Hepatitis B virus (HBV) chronic infections remain a considerable health problem worldwide. The standard therapies have demonstrated limited efficacy, side effects or need life-long treatments. Nowadays therapeutic vaccination is a promising option. Recently, we developed a new vaccine formulation called Nasvac, based on the combination of surface and core antigens from HBV. Clinical trials already performed showed good efficacy in virus control. However, the exact mode of action of Nasvac formulation remains unclear. So far the functional impairment of DCs during persistent HBV infection is a controversial issue. On the other hand, it is known that B cells may function as antigen presenting cells (APC) activating T cells. The hepatitis B core antigen contained in Nasvac vaccine is able to bind and activate a high frequency of naive human B cells. In the present study the surface expression of activation and exhaustion markers on B cells and the subsequent activation of T cells after in vitro stimulation with Nasvac antigens were evaluated in chronic HBV patients and healthy donors. B- and T-cell phenotype and proliferation were assessed by flow cytometry. Our results indicate that in contrast to exhaustions markers B cell activation markers were increased on both study groups after Nasvac stimulation. A shift toward an activation phenotype was observed for both B and T cells. The present work suggests that B cells could act as efficient APCs for Nasvac antigens in humans, which might suggest the use of activated B cells as immunotherapeutic strategy for chronic hepatitis B.

KW - B-Lymphocytes/cytology

KW - Biomarkers/metabolism

KW - Cell Proliferation

KW - Female

KW - Hepatitis B Vaccines/immunology

KW - Hepatitis B virus/immunology

KW - Hepatitis B, Chronic/immunology

KW - Humans

KW - Lymphocyte Activation/immunology

KW - Male

KW - T-Lymphocytes/cytology

KW - Tissue Donors

U2 - 10.1016/j.molimm.2014.08.003

DO - 10.1016/j.molimm.2014.08.003

M3 - SCORING: Journal article

C2 - 25193323

VL - 63

SP - 320

EP - 327

JO - MOL IMMUNOL

JF - MOL IMMUNOL

SN - 0161-5890

IS - 2

ER -