Immunogenicity of papaya mosaic virus-like particles fused to a hepatitis C virus epitope: Evidence for the critical function of multimerization
Immunogenicity of papaya mosaic virus-like particles fused to a hepatitis C virus epitope: Evidence for the critical function of multimerization
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DOI：
10.1016/j.virol.2007.01.011
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发表时间：
2007-06-20
期刊：
影响因子：
3.7
通讯作者：
Leclerc, Denis
中科院分区：
文献类型：
--
作者：
Denis, Jerome;Majeau, Nathalie;Leclerc, Denis
基于植物病毒的疫苗已经成为疫苗开发的一个有希望的途径。本文介绍了以木瓜花叶病毒（PapMV）衣壳蛋白（CP）为载体蛋白，C端融合型丙型肝炎病毒（HCV） E2表位为免疫原性靶点的创新疫苗平台的工程设计。对两种基于papmvv的疫苗抗原组织进行了测试：病毒样颗粒（VLP; PapMVCP-E2）和单体形式（PapMVCP(27-215)-E2）。虽然这两种形式的疫苗都被证明在体外骨髓源性抗原呈递细胞（APCs）中被积极内化，但免疫原性被证明强烈依赖于抗原组织。事实上，两次注射多聚VLP疫苗的C3H/HeJ小鼠对CP和融合的HCV E2表位均表现出持久的体液应答（超过120天）。抗体谱（IgG I, IgG2a, IgG2b， IgG3的产生）提示Th1 /Th2应答。当注入单体PapMVCP-E2时，未观察到PapMV疫苗平台的免疫原性。这些结果首次证明了PapMV疫苗平台的潜力和多聚化在其免疫原性中的关键功能。(C) 2007爱思唯尔公司版权所有。
Plant-virus-based vaccines have emerged as a promising avenue in vaccine development. This report describes the engineering of an innovative vaccine platform using the papaya mosaic virus (PapMV) capsid protein (CP) as a carrier protein and a C-terminal fused hepatitis C virus (HCV) E2 epitope as the immunogenic target. Two antigen organizations of the PapMV-based vaccines were tested: a virus-like-particle (VLP; PapMVCP-E2) and a monomeric form (PapMVCP(27-215)-E2). While the two forms of the vaccine were both shown to be actively internalized in vitro in bone-marrow-derived antigen presenting cells (APCs), inummogenicity was demonstrated to be strongly dependent on antigen organization. Indeed, C3H/HeJ mice injected twice with the multimeric VLP vaccine showed a long-lasting humoral response (more than 120 days) against both the CP and the fused HCV E2 epitope. The antibody profile (production of IgG I, IgG2a, IgG2b, IgG3) suggests a Th1 /Th2 response. Immunogenicity of the PapMV vaccine platform was not observed when the monomer PapMVCP-E2 was injected. These results demonstrate for the first time the potential of the PapMV vaccine platform and the critical function of multimerization in its immunogenicity. (C) 2007 Elsevier Inc. All rights reserved.