Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers
Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers
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DOI：
10.1073/pnas.94.4.1396
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发表时间：
1997-02-18
影响因子：
11.1
通讯作者：
Weinhold, KJ
中科院分区：
文献类型：
--
作者：
Ferrari, G;Humphrey, W;Weinhold, KJ
目前开发有效的艾滋病疫苗的策略的基本目标是引发能够破坏病毒感染的靶的广泛反应性细胞毒性T淋巴细胞（CTL）反应。最近将重组金丝雀痘ALVAC/HIV-1载体作为疫苗免疫原应用于HIV-1未感染的志愿者中，在相当数量的疫苗接种者中产生了CTL应答。我们检测了疫苗诱导的CTL裂解被不同病毒分离物感染的自体靶的能力。发现来自金丝雀痘ALVAC/HIV-1 gp 160（MN）疫苗接种者的CTL能够裂解感染HIV-1原型LAI株的自体CD 4（+）淋巴母细胞。当针对用代表遗传多样性病毒进化枝的原代HIV-1分离株感染的自体靶进行测试时，来自ALVAC/gp 160接受者的CTL显示出广泛的细胞溶解模式，其中识别来自所有测试进化枝的病毒，以及高度限制的模式，其中没有原代分离株，包括进化枝B，被溶解，用包膜载体免疫的志愿者的HLA单倍型的差异可能是其CTL应答的相对宽度的主要决定因素。与ALVAC/gp 160疫苗接种者相反，含有包膜以及gag和蛋白酶基因的ALVAC/HIV-1免疫原的接受者始终具有有效对抗一系列初级分离物感染的靶的CTL反应性，这些研究首次证明，基于进化枝B的金丝雀痘疫苗可以引起广泛的CTL反应性，能够识别属于遗传多样性HIV-1的病毒。结果还加强了疫苗中病毒核心元件的影响以及疫苗接受者在确定细胞应答的相对宽度中的主要组织相容性复合物I类等位基因表达的模式。
A fundamental goal of current strategies to develop an efficacious vaccine for AIDS is the elicitation of broadly reactive cytotoxic T lymphocyte (CTL) reactivities capable of destroying virally infected targets, Recent application of recombinant canarypox ALVAC/HIV-1 vectors as vaccine immunogens in HIV-1, -noninfected volunteers has produced CTL responses in a significant number of vaccinees, Using a newly developed targeting strategy, we examined the capacity of vaccine-induced CTL to lyse autologous targets infected with a diverse group of viral isolates. CTL derived from recipients of a canarypox ALVAC/HIV-1 gp160 (MN) vaccine were found capable of lysing autologous CD4(+) lymphoblasts infected with the prototypic LAI strain of HIV-1. When tested against autologous targets infected with primary HIV-1 isolates representing genetically diverse vira clades, CTL from ALVAC/gp160 recipients showed both a broad pattern of cytolysis in which viruses from all clades tested were recognized as well as a highly restricted pattern in which no primary isolates, including clade B, were lysed, Differences in the HLA haplotypes of the volunteers immunized with the envelope vector might be a major determinant of the relative breadth of their CTL response, In contrast to ALVAC/gp160 vaccinees, recipients of the ALVAC/HIV-1 immunogen containing envelope as well as gag and protease genes consistently had CTL reactivities effective against a spectrum of primary isolate-infected targets, These studies demonstrate for the first time that clade B-based canarypox vaccines can elicit broad CTL reactivities capable of recognizing viruses belonging to genetically diverse HIV-1 clades, The results also reinforce the impact of viral core elements in the vaccine as well as the pattern of major histocompatibility complex class I allelic expression by the vaccine recipient in determining the relative breadth of the cellular response.