Enhancement of SIV-specific cell mediated immune responses by co-administration of soluble PD-1 and Tim-3 as molecular adjuvants in mice
Enhancement of SIV-specific cell mediated immune responses by co-administration of soluble PD-1 and Tim-3 as molecular adjuvants in mice
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通过可溶性 PD-1 和 Tim-3 作为分子佐剂共同给药小鼠增强 SIV 特异性细胞介导的免疫反应
DOI：
10.4161/hv.27340
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Chen Ling
中科院分区：
文献类型：
--
作者：
Li Pingchao;Jin Yi;Feng Liqiang;Chen Ling
有效的基于T细胞的HIV疫苗的开发将需要引发具有上级幅度、广度和质量的细胞介导的免疫应答。由于使用可溶性PD-1（sPD-1）和可溶性Tim-3（sTim-3）阻断抑制性受体与其相关配体之间的相互作用已显示逆转T细胞耗竭并增强细胞介导的免疫应答，我们测试了sPD-1和sTim-3与腺病毒载体的SIV疫苗（rAd 5-SIV）的共同施用是否可以增强细胞介导的免疫应答。当在sPD-1或sTim-3或sPD-1和sTim-3两者存在下用SIV肽离体刺激时，来自rAd 5-SIV免疫的小鼠的SIV抗原特异性IFN-γ斑点形成细胞的频率以及脾细胞分泌IFN-γ和TNF-α显著增加。由rAd 5-SIV引起的细胞介导的免疫应答的幅度通过共同施用sPD-1和sTim-3而增强。共同施用sPD-1和sTim-3诱导SIV抗原特异性IFN-γ+斑点形成细胞的频率高于免疫原性差的Vif和达特。对每种SIV抗原的细胞介导反应百分比变得更加平衡，Gag减少，但非结构蛋白诱导。rAd 5-SIV与rAd 5-sPD 1、rAd 5-sTim 3共注射可增强小鼠T细胞增殖能力，产生更多抗原特异性IFN-γ+ CD 4+和CD 8 + T细胞。本研究为增强疫苗诱导的细胞免疫应答提供了一种新的途径，可能适用于提高SIV/HIV疫苗的效力。
The development of an effective T cell based HIV vaccine would need to elicit cell mediated immune responses with superior magnitude, breadth, and quality. Since blocking the interactions between inhibitory receptors with their associated ligands using soluble PD-1 (sPD-1) and soluble Tim-3 (sTim-3) have been shown to reverse T cell exhaustion and enhance cell mediated immune responses, we tested if co-administration of sPD-1 and sTim-3 with an adenovirus vectored SIV vaccine (rAd5-SIV) can enhance cell mediated immune responses. The frequency of SIV antigen specific IFN-γ spot-forming cells and the secretion of IFN-γ and TNF-α by splenocytes from rAd5-SIV immunized mice was significantly increased when stimulated ex vivo with SIV peptides in the presence of sPD-1 or sTim-3 or both sPD-1 and sTim-3. The magnitude of cell mediated immune responses elicited by rAd5-SIV was enhanced by co-administration of sPD-1 and sTim-3. Co-administration of both sPD-1 and sTim-3 induced higher frequency of SIV antigen specific IFN-γ+ spot-forming cells to poorly immunogenic Vif and Tat. The percentage of cell mediated responses for each SIV antigen became more balanced, with reduction to Gag but induction to non-structural proteins. Furthermore, co-injection of rAd5-sPD1 and rAd5-sTim3 with rAd5-SIV in mice enhanced T cell proliferation capability and generated more antigen specific IFN-γ+ CD4+ and CD8+ T cells. Our study provided a new approach to enhance vaccine induced cell mediated immune responses, which may be applicable to improve the efficacy of vaccines against SIV/HIV.
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DOI：
10.4172/2155-9899.s7-007
发表时间：
2013
期刊：
Journal of clinical & cellular immunology
影响因子：
--
作者：
A. Rahman;K. Clayton;S. Mujib;I. Fong;M. Ostrowski
通讯作者：
A. Rahman;K. Clayton;S. Mujib;I. Fong;M. Ostrowski
影响因子：
6.7
作者：
Sehrawat S;Reddy PB;Rajasagi N;Suryawanshi A;Hirashima M;Rouse BT
通讯作者：
Rouse BT
影响因子：
5.4
作者：
Casimiro, DR;Tang, AM;Shiver, JW
通讯作者：
Shiver, JW
影响因子：
30.5
作者：
Sabatos, CA;Chakravarti, S;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1073/pnas.84.19.6869
发表时间：
1987-10-01
影响因子：
11.1
作者：
JOHANSSON, BE;MORAN, TM;KILBOURNE, ED
通讯作者：
KILBOURNE, ED