Human cytotoxic T lymphocyte responses to live attenuated 17D yellow fever vaccine: Identification of HLA-1335-restricted CTL epitopes on nonstructural proteins NS1, NS2b, NS3, and the structural protein E

Human cytotoxic T lymphocyte responses to live attenuated 17D yellow fever vaccine: Identification of HLA-1335-restricted CTL epitopes on nonstructural proteins NS1, NS2b, NS3, and the structural protein E
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DOI:
10.1006/viro.2001.1255
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发表时间:
2002-02-01
期刊:
影响因子:
3.7
通讯作者:
Rothman, AL
Rothman, AL
中科院分区:
医学3区
文献类型:
--
作者:
Co, MDT;Terajima, M;Rothman, AL

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尽管存在有效的减毒活疫苗,黄热病病毒(YFV)仍是一个新出现的问题。YFV中和抗体的诱导无疑有助于疫苗的疗效,但对YFV的T淋巴细胞反应可能在长期疗效中发挥作用。我们研究了四名疫苗接种者对YFV的T淋巴细胞反应。所有受试者均表现出对YFV的增殖和细胞溶解反应。我们分离了13个识别E、NS1、NS2b和NS3蛋白表位的YFV特异性CD8‘CTL株,其中8个CTL株是人类白细胞抗原B35限制性的。免疫后14天,IFNGamma ELISPOT检测可检测到YFV特异性T细胞反应,T细胞频率可持续长达19个月。据我们所知,这是YFV疫苗接种后人类T淋巴细胞反应的第一次报告。这些结果表明,17D YFV活疫苗可诱导针对至少4个不同的HLAB35限制性YFV表位的CD8(-)T细胞反应。(C)2002年埃尔塞维尔科学公司(美国)。
Yellow fever virus (YFV) is a reemerging problem despite the existence of an effective live-attenuated vaccine. The induction of YFV-neutralizing antibodies undoubtedly contributes to vaccine efficacy, but T lymphocyte responses to YFV likely play a role in long-term efficacy. We studied the T lymphocyte responses to YFV in four vaccinees. Proliferation and cytolytic responses to YFV were demonstrated in all subjects. We isolated 13 YFV-specific CD8' CTL lines that recognized epitopes on the E, NS1, NS2b, and NS3 proteins; eight CTL lines were HLA-B35-restricted. YFV-specific T cell responses were detectable by IFNgamma ELISPOT assays 14 days postvaccination, with T cell frequencies sustained for up to 19 months. To our knowledge, this is the first report of human T lymphocyte responses following YFV vaccination. These results indicate that the live 17D YFV vaccine induced CD8(-) T cell responses directed against at least four different HLA-B35-restricted YFV epitopes. (C) 2002 Elsevier Science (USA).