4-1BBL coexpression enhances HIV-specific CD8 T cell memory in a poxvirus prime-boost vaccine

4-1BBL coexpression enhances HIV-specific CD8 T cell memory in a poxvirus prime-boost vaccine
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DOI:
10.1016/j.vaccine.2006.06.007
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发表时间:
2006-11-17
期刊:
影响因子:
5.5
通讯作者:
Ramshaw, Ian A.
Ramshaw, Ian A.
中科院分区:
医学3区
文献类型:
--
作者:
Harrison, Jodie M.;Bertram, Edward M.;Ramshaw, Ian A.

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我们构建了表达HIV抗原和共刺激分子4-1 BBL的重组禽痘病毒。通过体外IFN γ ELISPOT反应、细胞内细胞因子对HIV Gag抗原的染色和Gag反应性CD8 T细胞计数检测,当被纳入增强剂而不是痘病毒启动剂-增强策略的启动剂时,4-1BBL显著增强了BALB/c小鼠对该疫苗产生的抗HIV T细胞应答。然而,4-1BBL不能调节CD4 T细胞反应,也不能调节抗体对这种疫苗接种策略的反应。在接种疫苗2个月后检测到,4-1 BBL的T细胞反应增强持续到记忆期。这一数据首次显示了通过4-1BBL的共表达来调节对病毒疫苗的免疫反应,并支持这一策略作为一种令人兴奋的方法来增强初级增强疫苗中的T细胞记忆。(c) 2006 Elsevier Ltd.版权所有。
We have constructed a recombinant fowlpox virus expressing HIV antigens and the costimulatory molecule 4-1 BBL. When included in the boost, but not the prime of a poxvirus prime-boost strategy, 4-1BBL significantly enhanced the anti-HIV T cell response generated to this vaccination in BALB/c mice, as detected by ex vivo IFN gamma ELISPOT responses, intracellular cytokine staining to HIV Gag antigens, and enumeration of Gag-reactive CD8 T cells. 4-1BBL however, is not capable of modulating the CD4 T cell response, nor the antibody response to this vaccination strategy. Enhancement of the T cell response by 4-1 BBL continues into the memory phase, as detected 2 months post vaccination. This data is the first to show modulation of the immune response to a viral vaccine by coexpression of 4-1BBL and supports this strategy as an exciting approach for enhancement of T cell memory in prime-boost vaccines. (c) 2006 Elsevier Ltd. All rights reserved.