Lobaina Yadira, Hardtke Svenja, Wedemeyer Heiner, Aguilar Julio Cesar, Schlaphoff Verena
Hepatitis B Therapeutic Vaccine Department, Biomedical Research, Center for Genetic Engineering and Biotechnology, Havana 10600, Cuba.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg StraBe 1, D-30625 Hannover, Germany.
Mol Immunol. 2015 Feb;63(2):320-7. doi: 10.1016/j.molimm.2014.08.003. Epub 2014 Sep 2.
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.
乙型肝炎病毒（HBV）慢性感染仍是全球范围内一个相当严重的健康问题。标准疗法已显示出疗效有限、有副作用或需要终身治疗。如今，治疗性疫苗接种是一个有前景的选择。最近，我们开发了一种名为Nasvac的新疫苗制剂，它基于HBV的表面抗原和核心抗原的组合。已进行的临床试验显示在病毒控制方面有良好疗效。然而，Nasvac制剂的确切作用方式仍不清楚。到目前为止，持续性HBV感染期间树突状细胞（DC）的功能损伤是一个有争议的问题。另一方面，已知B细胞可能作为抗原呈递细胞（APC）激活T细胞。Nasvac疫苗中含有的乙型肝炎核心抗原能够结合并激活高频率的未活化人类B细胞。在本研究中，在慢性HBV患者和健康供体中评估了用Nasvac抗原体外刺激后B细胞上激活和耗竭标志物的表面表达以及随后T细胞的激活情况。通过流式细胞术评估B细胞和T细胞的表型及增殖情况。我们的结果表明，与耗竭标志物相反，在Nasvac刺激后两个研究组中B细胞激活标志物均增加。观察到B细胞和T细胞均向激活表型转变。目前的工作表明，B细胞可能作为人类中Nasvac抗原的有效APC，这可能提示将活化的B细胞用作慢性乙型肝炎的免疫治疗策略。
