Protective attenuated lentivirus immunization induces SIV-specific T cells in the genital tract of rhesus monkeys

Protective attenuated lentivirus immunization induces SIV-specific T cells in the genital tract of rhesus monkeys
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DOI:
10.1038/mi.2008.6
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发表时间:
2008-05-01
期刊:
影响因子:
8
通讯作者:
Miller, C. J.
Miller, C. J.
中科院分区:
医学1区
文献类型:
--
作者:
Genesca, M.;Skinner, P. J.;Miller, C. J.

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慢病毒减毒活免疫是唯一一种能够持续抵抗致病性猴免疫缺陷病毒(SIV)阴道内攻击的疫苗策略。为了确定感染减毒猿人免疫缺陷病毒(SHIV)89.6的恒河猴的保护机制,详细分析了SIV gag特异性t细胞在包括生殖道在内的几种组织中的反应。hiv感染6个月后,宫颈中很少出现抗病毒t细胞反应;然而,在免疫的猕猴的阴道中一致发现了多功能、细胞因子分泌和脱颗粒SIV gag特异性CD4(+) T细胞。在大多数动物的阴道、血液和生殖器淋巴结中也检测到siv特异性CD8(+) T细胞。因此,减毒的SHIV疫苗在包括阴道在内的组织中诱导持久的抗病毒T细胞,在该模型中观察到,这些效应T细胞反应可能介导对阴道SIV攻击的一致保护。
Live attenuated lentivirus immunization is the only vaccine strategy that elicits consistent protection against intravaginal challenge with pathogenic simian immunodeficiency virus (SIV). To determine the mechanism of protection in rhesus monkeys infected with attenuated simian-human immunodeficiency virus (SHIV)89.6,a detailed analysis of SIV Gag-specific T-cell responses in several tissues including the genital tract was performed. Six months after SHIV infection, antiviral T-cell responses were rare in the cervix; however, polyfunctional, cytokine-secreting, and degranulating SIV Gag-specific CD4(+) T cells were consistently found in the vagina of the immunized macaques. SIV-specific CD8(+) T cells were also detected in the vagina, blood, and genital lymph nodes of most of the animals. Thus, an attenuated SHIV vaccine induces persistent antiviral T cells in tissues, including the vagina, where these effector T-cell responses may mediate the consistent protection from vaginal SIV challenge observed in this model.