Highly Efficient Antiviral CD8+ T-Cell Induction by Peptides Coupled to the Surfaces of Liposomes
Highly Efficient Antiviral CD8+ T-Cell Induction by Peptides Coupled to the Surfaces of Liposomes
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通过与脂质体表面偶联的肽诱导高效抗病毒 CD8 T 细胞
DOI：
10.1128/cvi.00116-09
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发表时间：
2009
影响因子：
--
通讯作者：
T. Akatsuka
中科院分区：
文献类型：
--
作者：
A. Takagi;M. Matsui;S. Ohno;Hongying Duan;O. Moriya;Nobuharu Kobayashi;H. Oda;M. Mori;Akiharu Kobayashi;M. Taneichi;T. Uchida;T. Akatsuka
在之前的研究中，我们已经证明，当抗原（Ags）与它们的表面化学偶联时，具有不同脂质成分的脂质体表现出不同的佐剂作用。当卵清蛋白与不饱和脂肪酸脂质体偶联时，发现它不仅能呈献给CD4+ T细胞，还能呈献给CD8+ T细胞并诱导细胞毒性T淋巴细胞（ctl），有效地根除小鼠肿瘤。在这项研究中，我们将脂质体与淋巴细胞性脉络丛脑膜炎病毒（LCMV）的免疫显性CTL表位肽偶联，并评估其作为抗病毒疫苗的效力。用肽脂质体与CpG结合物对小鼠进行肌肉免疫，可有效诱导抗病毒CD8+ t细胞反应，不仅能完全保护小鼠免受LCMV Armstrong感染，还能抵抗一种高毒力突变株（克隆13），该突变株可在免疫能力强的小鼠中建立持续感染。鼻内疫苗接种诱导的粘膜免疫足够有效地保护小鼠免受病毒通过相同途径的攻击。即使将银剂量降至280 ng的脂质体肽，小鼠也能获得完全的保护。在没有CD4+ T细胞帮助的情况下，这种单一CTL表位的疫苗接种形式诱导了ag特异性记忆CD8+ T细胞，这可以通过CD4敲除小鼠在10周内的完全保护以及回忆反应的分析来证明。因此，表面连接脂质体肽可能具有诱导抗病毒免疫的潜在优势。
ABSTRACT In previous studies, we have demonstrated that liposomes with differential lipid components display differential adjuvant effects when antigens (Ags) are chemically coupled to their surfaces. When ovalbumin was coupled to liposomes made by using unsaturated fatty acids, it was found to be presented not only to CD4+ T cells but also to CD8+ T cells and induced cytotoxic T lymphocytes (CTLs) which effectively eradicated the tumor from mice. In this study, we coupled liposomes to immunodominant CTL epitope peptides derived from lymphocytic choriomeningitis virus (LCMV) and evaluated its potency as an antiviral vaccine. The intramuscular immunization of mice with the peptide-liposome conjugates along with CpG resulted in the efficient induction of antiviral CD8+ T-cell responses which conferred complete protection against not only LCMV Armstrong but also a highly virulent mutant strain, clone 13, that establishes persistent infections in immunocompetent mice. The intranasal vaccination induced mucosal immunity effective enough to protect mice from the virus challenge via the same route. Complete protection was achieved in mice even when the Ag dose was reduced to as low as 280 ng of liposomal peptide. This form of vaccination with a single CTL epitope induced Ag-specific memory CD8+ T cells in the absence of CD4+ T-cell help, which could be shown by the complete protection of CD4-knockout mice in 10 weeks as well as by the analysis of recall responses. Thus, surface-linked liposomal peptide might have a potential advantage for the induction of antiviral immunity.
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DOI：
10.1073/pnas.92.9.3987
发表时间：
1995-04-25
影响因子：
11.1
作者：
SHEN, H;SLIFKA, MK;MILLER, JF
通讯作者：
MILLER, JF
影响因子：
5.4
作者：
Wherry, EJ;Blattman, JN;Ahmed, R
通讯作者：
Ahmed, R
DOI：
10.1084/jem.20071949
发表时间：
2008-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ha SJ;Mueller SN;Wherry EJ;Barber DL;Aubert RD;Sharpe AH;Freeman GJ;Ahmed R
通讯作者：
Ahmed R
影响因子：
32.4
作者：
Guidotti, LG;Ishikawa, T;Chisari, FV
通讯作者：
Chisari, FV
质粒 DNA 疫苗在没有 IFNgamma 的情况下也有效。
DOI：
10.1006/viro.1999.9957
发表时间：
1999
期刊：
Virology.
影响因子：
--
作者：
Hassett,DE;Zhang,J;Whitton,JL
通讯作者：
Whitton,JL