Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7.
Anti-IgE Qb-VLP Conjugate Vaccine Self-Adjuvants through Activation of TLR7.
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DOI：
10.3390/vaccines4010003
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发表时间：
2016-01-21
期刊：
影响因子：
7.8
通讯作者：
McCluskie MJ
中科院分区：
文献类型：
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作者：
Akache B;Weeratna RD;Deora A;Thorn JM;Champion B;Merson JR;Davis HL;McCluskie MJ
Qb噬菌体病毒样颗粒（Qb-VLP）被用作载体以增强对弱或非免疫原性抗原如肽和半抗原的免疫应答。Qb-VLP是通过多个Qb衣壳蛋白单体的自组装形成的，该过程将大量细菌RNA捕获在VLP的核心中。已知细菌RNA通过在某些免疫细胞的内体中发现的TLR 7和8激活先天免疫系统，并且已显示有助于Qb-VLP疫苗的免疫原性。在此，我们评估了由与Qb-VLP（分别为Qb-Y和Qb-P）缀合的两种IgE肽（Y和P）组成的抗IgE疫苗对人PBMC的体外刺激和小鼠中的体内免疫原性。来自暴露于Qb-Y的人PBMC的IFN-α的体外分泌与TLR 7活化一致。用IgE肽Qb-VLP缀合物免疫小鼠在野生型小鼠中诱导高滴度的抗IgE抗体，但在TLR 7敲除小鼠中显著较低滴度，支持RNA的自我辅助作用。包含明矾和明矾/CpG作为佐剂部分或完全补偿了TLR 7缺陷小鼠中TLR 7活化的缺乏。我们的研究证明了TLR 7在IgE肽Qb-VLP缀合物疫苗的免疫原性中起关键作用。
Qb bacteriophage virus-like particles (Qb-VLP) are utilized as carriers to enhance immune responses to weakly or non-immunogenic antigens such as peptides and haptens. Qb-VLPs are formed through the self-assembly of multiple Qb capsid protein monomers, a process which traps a large amount of bacterial RNA in the core of the VLP. Bacterial RNA is known to activate the innate immune system via TLR 7 and 8 found within the endosomes of certain immune cells and has been shown to contribute to the immunogenicity of Qb-VLP vaccines. Herein, we evaluated an anti-IgE vaccine comprised of two IgE peptides (Y and P) conjugated to Qb-VLP (Qb-Y and Qb-P, respectively) for in vitro stimulation of human PBMCs and in vivo immunogenicity in mice. The in vitro secretion of IFN-α from human PBMCs exposed to Qb-Y is consistent with TLR7 activation. Immunization of mice with the IgE peptide Qb-VLP conjugates induced high titers of anti-IgE antibodies in wild-type mice, but significantly lower titers in TLR7 knockout mice, supporting the self-adjuvanting role of the RNA. Inclusion of alum and alum/CpG as adjuvants partially or completely compensated for the lack of TLR7 activation in TLR7-deficient mice. Our study demonstrates the key role that TLR7 plays in the immunogenicity of the IgE peptide Qb-VLP conjugate vaccine.