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基于细胞毒性 T 淋巴细胞的、广泛保护性流感疫苗的研制。

Development of a cytotoxic T-lymphocyte-based, broadly protective influenza vaccine.

机构信息

Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Musashimurayama-City, Tokyo, Japan.

出版信息

Microbiol Immunol. 2011 Jan;55(1):19-27. doi: 10.1111/j.1348-0421.2010.00273.x.

Abstract

The current vaccination strategy against influenza is to induce production of antibodies directed against the surface antigens of these viruses. However, frequent changes in the surface antigens of influenza viruses allow them to avoid antibody-mediated immunity. On the other hand, it is known that cytotoxic T-lymphocyte (CTL) populations directed against internal antigens of influenza A virus are broadly cross-reactive to influenza virus subtypes. The present authors have previously demonstrated that antigens chemically coupled to the surface of liposomes made using unsaturated fatty acids are cross-presented by APCs via MHC class I to CD8(+) T cells and induce antigen-specific CTLs. Based on this finding, a liposome vaccine that is capable of inducing CTL response against internal antigens of influenza viruses and removing virus-infected cells in the host has been developed. The CTL-based liposomal technique might be applicable for developing vaccines against influenza and other viruses, such as hepatitis C, HIV, and severe acute respiratory syndrome corona virus, which frequently change their surface antigenic molecules.

摘要

目前针对流感的疫苗接种策略是诱导针对这些病毒表面抗原的抗体产生。然而,流感病毒表面抗原的频繁变化使其能够逃避抗体介导的免疫。另一方面,人们已经知道针对流感 A 病毒内部抗原的细胞毒性 T 淋巴细胞 (CTL) 群体广泛交叉反应于流感病毒亚型。作者先前已经证明,化学偶联到使用不饱和脂肪酸制成的脂质体表面的抗原可通过 MHC Ⅰ类被 APC 交叉呈递给 CD8(+) T 细胞,并诱导抗原特异性 CTL。基于这一发现,已经开发出一种能够诱导针对流感病毒内部抗原的 CTL 反应并清除宿主中病毒感染细胞的脂质体疫苗。基于 CTL 的脂质体技术可能适用于开发针对流感和其他病毒(如丙型肝炎、HIV 和严重急性呼吸综合征冠状病毒)的疫苗,这些病毒经常改变其表面抗原分子。

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