A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses
A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses
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DOI：
10.1016/s0264-410x(02)00266-9
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发表时间：
2002-08-19
期刊：
影响因子：
5.5
通讯作者：
Bachmann, MF
中科院分区：
文献类型：
--
作者：
Jegerlehner, A;Tissot, A;Bachmann, MF
已知病毒样颗粒（VLP）在不存在佐剂的情况下可诱导有效的B细胞反应。此外，表位特异性抗体应答可由含有插入其免疫显性区域中的肽的VLP诱导。然而，由于空间问题，能够掺入VLP同时仍允许衣壳组装的肽的大小相当有限。虽然与VLP的N-或C-末端基因融合的肽存在较少的组装问题，但针对这些表位获得的免疫应答通常是有限的，最可能是因为表位没有最佳地暴露。此外，这样的颗粒在体内可能不太稳定。在这里，我们表明，肽和蛋白质工程包含一个免费的半胱氨酸可以化学偶联到VLP形成的B型肝炎核心抗原（HBcAg）含有一个赖氨酸的免疫优势区。通过使用这种方法，消除了衣壳组装的空间位阻。以定向方式偶联至VLP的肽或蛋白质显示在没有佐剂的情况下甚至针对自身表位诱导强的和保护性的B细胞应答。该分子组装系统可用于诱导针对大多数抗原的强B细胞应答。(C)2002爱思唯尔科技有限公司版权所有。
Virus like particles (VLPs) are known to induce potent B cell responses in the absence of adjuvants. Moreover, epitope-specific antibody responses may be induced by VLPs that contain peptides inserted in their immunodominant regions. However, due to steric problems, the size of the peptides capable of being incorporated into VLPs while still permitting capsid assembly, is rather limited. While peptides genetically fused to either the N- or C-terminus of VLPs present fewer assembly problems, the immune responses obtained against such epitopes are often limited, most likely because the epitopes are not optimally exposed. In addition, such particles may be less stable in vivo. Here, we show that peptides and proteins engineered to contain a free cys can be chemically coupled to VLPs formed from the hepatitis B core antigen (HBcAg) containing a lys in the immuno-dominant region. By using this approach steric hindrance of capsid assembly is abrogated. Peptides or protein coupled to VLPs in an oriented fashion are shown to induce strong and protective B cell responses even against self-epitopes in the absence of adjuvants. This molecular assembly system may be used to induce strong B cell responses against most antigens. (C) 2002 Elsevier Science Ltd. All rights reserved.