Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants
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DOI:
10.1016/j.virol.2013.10.010
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发表时间:
2014-01-05
期刊:
影响因子:
3.7
通讯作者:
Matsui, Masanori
Matsui, Masanori
中科院分区:
医学3区
文献类型:
--
作者:
Kawano, Masaaki;Morikawa, Katsuma;Matsui, Masanori

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由于安全性和有效性,病毒样颗粒(VLP)是一种有前途的疫苗平台。然而,目前尚不清楚基于多瘤病毒的 VLP 是否可用于此目的。在这里,我们尝试使用猿猴病毒 40 (SV40) 评估多瘤病毒 VLP 用于抗病毒疫苗的潜力。我们构建了嵌合 SV40-VLP,其携带源自甲型流感病毒的 HLA-A*02:01 限制性细胞毒性 T 淋巴细胞 (CTL) 表位。然后用嵌合SV40-VLP免疫HLA-A*02:01转基因小鼠。嵌合 SV40-VLP 无需佐剂即可有效诱导流感特异性 CTL 和针对甲型流感病毒的异亚型保护。由于嵌合 SV40-VLP 的 DNase I 处理不会破坏 CTL 诱导,因此固有的佐剂特性可能不是由 VLP 制剂中的 DNA 污染物造成的。此外,用嵌合 SV40-VLP 进行免疫会产生持久的记忆 CTL。我们在此提出,含有表位的嵌合 SV40-VLP 可能是一种有前景的具有自我佐剂特性的基于 CTL 的疫苗平台。 (C) 2013 Elsevier Inc. 保留所有权利。
Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A*02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A*02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. (C) 2013 Elsevier Inc. All rights reserved.