A dual TLR agonist adjuvant enhances the immunogenicity and protective efficacy of the tuberculosis vaccine antigen ID93.
A dual TLR agonist adjuvant enhances the immunogenicity and protective efficacy of the tuberculosis vaccine antigen ID93.
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DOI：
10.1371/journal.pone.0083884
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Coler RN
中科院分区：
文献类型：
--
作者：
Orr MT;Beebe EA;Hudson TE;Moon JJ;Fox CB;Reed SG;Coler RN
每年有超过800万例结核病病例，迫切需要开发针对结核分枝杆菌的新疫苗。由重组蛋白组成的亚单位疫苗是一种有吸引力的疫苗方法，这是由于与减毒活疫苗相比其固有的安全性和制造的一致性。向重组蛋白疫苗中添加适当配制的含有TLR激动剂的佐剂增强了以IFN-γ和TNF为特征的抗原特异性CD 4 + T细胞应答，这两者对于控制TB都是至关重要的。我们已经开发了一种临床阶段疫苗候选物，其由用TLR 4激动剂GLA-SE佐剂化的重组融合蛋白ID 93组成。在这里，我们检查是否可以通过添加第二TLR激动剂来改善ID 93 +GLA-SE。向ID 93 +GLA-SE中添加含有CpG的DNA增强了针对ID 93的多功能TH 1应答的幅度，其特征在于IFN-γ、TNF和IL-2的共产生。CpG的添加也改善了ID 93 +GLA-SE的保护功效。最后，我们证明了GLA和CpG之间的这种佐剂协同作用不依赖于TRIF信号传导，而TRIF是在不存在CpG的情况下GLA-SE的佐剂活性所必需的。
With over eight million cases of tuberculosis each year there is a pressing need for the development of new vaccines against Mycobacterium tuberculosis. Subunit vaccines consisting of recombinant proteins are an attractive vaccine approach due to their inherent safety compared to attenuated live vaccines and the uniformity of manufacture. Addition of properly formulated TLR agonist-containing adjuvants to recombinant protein vaccines enhances the antigen-specific CD4+ T cell response characterized by IFN-γ and TNF, both of which are critical for the control of TB. We have developed a clinical stage vaccine candidate consisting of a recombinant fusion protein ID93 adjuvanted with the TLR4 agonist GLA-SE. Here we examine whether ID93+GLA-SE can be improved by the addition of a second TLR agonist. Addition of CpG containing DNA to ID93+GLA-SE enhanced the magnitude of the multi-functional TH1 response against ID93 characterized by co-production of IFN-γ, TNF, and IL-2. Addition of CpG also improved the protective efficacy of ID93+GLA-SE. Finally we demonstrate that this adjuvant synergy between GLA and CpG is independent of TRIF signaling, whereas TRIF is necessary for the adjuvant activity of GLA-SE in the absence of CpG.
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影响因子：
6.7
作者：
Hajjar AM;Ernst RK;Fortuno ES 3rd;Brasfield AS;Yam CS;Newlon LA;Kollmann TR;Miller SI;Wilson CB
通讯作者：
Wilson CB
DOI：
10.4049/jimmunol.1200601
发表时间：
2012-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Matthews K;Chung NP;Klasse PJ;Moore JP;Sanders RW
通讯作者：
Sanders RW
I型Interferon自分泌 - 核酸环与树突状细胞的Toll样受体诱导的白介素-12p70分泌有关。
影响因子：
15.3
作者：
Gautier, G;Humbert, M;Deauvieau, F;Scuiller, M;Hiscott, J;Bates, EEM;Trinchieri, G;Caux, C;Garrone, P
通讯作者：
Garrone, P
影响因子：
7.8
作者：
Manicassamy S;Pulendran B
通讯作者：
Pulendran B
DOI：
10.1073/pnas.0703510104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Mittruecker, Hans-Willi;Steinhoff, Ulrich;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.