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嵌合 SV40 病毒样颗粒在无需佐剂的情况下诱导针对甲型流感病毒的特异性细胞毒性和保护性免疫。

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

机构信息

Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495, Japan.

出版信息

Virology. 2014 Jan 5;448:159-67. doi: 10.1016/j.virol.2013.10.010. Epub 2013 Oct 25.

Abstract

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-A02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A02:01-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.

摘要

病毒样颗粒 (VLPs) 是一种很有前途的疫苗平台,因为它们既安全又高效。然而,目前尚不清楚基于多瘤病毒的 VLPs 是否对此有用。在这里,我们试图使用猿猴病毒 40 (SV40) 来评估多瘤病毒 VLPs 作为抗病毒疫苗的潜力。我们构建了携带来自甲型流感病毒的 HLA-A02:01 限制性细胞毒性 T 淋巴细胞 (CTL) 表位的嵌合 SV40-VLPs。然后,用嵌合 SV40-VLPs 免疫 HLA-A02:01 转基因小鼠。嵌合 SV40-VLPs 有效地诱导了流感特异性 CTL,并对甲型流感病毒具有异源保护作用,而无需佐剂。由于嵌合 SV40-VLPs 的 DNase I 处理不会破坏 CTL 的诱导,因此内在的佐剂特性可能不是来自 VLP 制备中的 DNA 污染物。此外,用嵌合 SV40-VLPs 免疫产生了持久的记忆 CTL。我们在此提出,携带表位的嵌合 SV40-VLPs 可能是一种具有自身佐剂特性的很有前途的基于 CTL 的疫苗平台。

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