The past, present and future of neutralizing antibodies for hepatitis C virus.

The past, present and future of neutralizing antibodies for hepatitis C virus.
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DOI:
10.1016/j.antiviral.2014.02.013
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发表时间:
2014-05
期刊:
影响因子:
7.6
通讯作者:
McKeating, Jane A.
McKeating, Jane A.
中科院分区:
医学2区
文献类型:
--
作者:
Ball, Jonathan K.;Tarr, Alexander W.;McKeating, Jane A.

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最近的研究已经深入了解了中和抗体在丙型肝炎中的保护作用。中和抗体对多种HCV基因型表现出广泛的反应性。重组HCV糖蛋白可引起中和抗体。HCV E2核心结构可为免疫原的合理设计提供依据。丙型肝炎病毒(HCV)是世界范围内肝脏疾病和肝细胞癌的主要病因。丙型肝炎病毒在大多数病例中形成慢性感染。然而,一些个体清除了病毒,显示出对宿主免疫反应的保护作用。尽管新的全口服药物组合可能很快取代传统的利巴韦林-干扰素治疗,但新出现的药物组合将会很昂贵,并且与副作用和耐药性有关,这使得全球疫苗成为当务之急。人们普遍认为T细胞在清除急性HCV感染中起着至关重要的作用,而抗体在解决和疾病发病机制中的作用却知之甚少。最近的研究提供了一个洞察病毒中和决定因素和抗体在感染期间的保护作用。这篇综述提供了中和抗体在HCV感染中的作用的历史观点,并讨论了基于抗体的治疗的治疗益处。这篇文章是抗病毒研究专题讨论会“丙型肝炎:全球根除的下一步”的一部分。
Recent studies have provided insight into the protective role of neutralizing antibodies in hepatitis C. Neutralizing antibodies show broad reactivity for diverse HCV genotypes. Recombinant HCV glycoproteins can elicit neutralizing antibodies. The HCV E2 core structure can inform rational design of immunogens. Hepatitis C virus (HCV) is a major cause of liver disease and hepatocellular carcinoma worldwide. HCV establishes a chronic infection in the majority of cases. However, some individuals clear the virus, demonstrating a protective role for the host immune response. Although new all-oral drug combinations may soon replace traditional ribavirin–interferon therapy, the emerging drug cocktails will be expensive and associated with side-effects and resistance, making a global vaccine an urgent priority. T cells are widely accepted to play an essential role in clearing acute HCV infection, whereas the role antibodies play in resolution and disease pathogenesis is less well understood. Recent studies have provided an insight into viral neutralizing determinants and the protective role of antibodies during infection. This review provides a historical perspective of the role neutralizing antibodies play in HCV infection and discusses the therapeutic benefits of antibody-based therapies. This article forms part of a symposium in Antiviral Research on “Hepatitis C: next steps toward global eradication.”
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