Intramuscular rather than oral administration of replication-defective adenoviral vaccine vector induces specific CD8+ T cell responses in the gut

Intramuscular rather than oral administration of replication-defective adenoviral vaccine vector induces specific CD8+ T cell responses in the gut
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DOI:
10.1016/j.vaccine.2006.11.044
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发表时间:
2007-03-08
期刊:
影响因子:
5.5
通讯作者:
Ertl, H. C.
Ertl, H. C.
中科院分区:
医学3区
文献类型:
--
作者:
Lin, S. W.;Cun, A. S.;Ertl, H. C.

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肠道相关淋巴组织 (GALT) 是 HIV-1 的主要复制位点,导致初次感染期间该组织中 CD4(+) T 细胞明显丧失。一种在肠道中产生 HIV 特异性 CD8(+) T 细胞的粘膜疫苗可以防止创始人群体的建立和病毒的传播。在这里,我们用表达 HIV gag (AdC68gag) 的黑猩猩衍生腺病毒载体对小鼠进行口服和全身免疫,并测量了 GALT 中产生 gag 特异性干扰素-γ (IFN-γ) 的 CD8+ T 细胞的频率。单次口服给药在引起肠系膜淋巴结和派尔氏淋巴结反应方面效率低下,而单次肌肉注射则引起强烈的全身性和可检测的粘膜反应。肌肉注射后,gag特异性CD8(+) T细胞反应出现在急性期和记忆期。 (c) 2006 Elsevier Ltd. 保留所有权利。
Gut-associated lymphoid tissue (GALT) is the primary replication site for HIV-1, resulting in a pronounced CD4(+) T cell loss in this tissue during primary infection. A mucosal vaccine that generates HIV-specific CD8(+) T cells in the gut could prevent the establishment of founder populations and broadcasting of virus. Here, we immunized mice orally and systemically with a chimpanzee derived adenoviral vector expressing HIV gag (AdC68gag) and measured frequencies of gag-specific interferon-gamma (IFN-gamma) producing CD8(+) T cells in the GALT. A single oral administration was inefficient at eliciting responses in the mesenteric lymph nodes and Peyer's Patches, while a single intramuscular administration elicited strong systemic and detectable mucosal responses. The gag-specific CD8(+) T cell responses were present in both acute and memory phases following intramuscular administration. (c) 2006 Elsevier Ltd. All rights reserved.