Inactivated influenza vaccine adjuvanted with Bacterium-like particles induce systemic and mucosal influenza A virus specific T-cell and B-cell responses after nasal administration in a TLR2 dependent fashion
Inactivated influenza vaccine adjuvanted with Bacterium-like particles induce systemic and mucosal influenza A virus specific T-cell and B-cell responses after nasal administration in a TLR2 dependent fashion
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DOI：
10.1016/j.vaccine.2014.02.019
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发表时间：
2014-05-19
期刊：
影响因子：
5.5
通讯作者：
Broere, F.
中科院分区：
文献类型：
--
作者：
Keijzer, C.;Haijema, B. J.;Broere, F.
背景：鼻疫苗接种被认为是一种有希望的非肠外流感病毒疫苗接种的替代方法，因为它是非侵入性的，并且有机会在病原体进入的口岸引发全身和局部强烈的抗原特异性反应。先前的研究表明，来自食品级细菌乳酸乳球菌的非活细菌样颗粒（BLPs）在鼻内给药时是局部和全身免疫反应的有效刺激物。此外，在体外，BLPs特异性地与人toll样受体2 （TLR2）相互作用，提示BLPs在TLR2依赖性免疫激活中的作用。方法：在本研究中，我们用TLR2敲除小鼠，检测了TLR2在经鼻给药BLP混合甲型流感病毒（IAV）分裂流感疫苗（BLP- sv）后的体内免疫激活中的作用。结果：鼻内接种BLP-SV后诱导的全身Th1细胞和随后的b细胞应答依赖于blp与TLR2的相互作用。值得注意的是，BLP- sv诱导的类切换到IgG2c取决于BLP与TLR2的相互作用。局部诱导的iav特异性Th1细胞反应和粘膜b细胞反应也依赖于BLP与TLR2的相互作用。在TLR2基因敲除小鼠的鼻腔和阴道灌洗液中均观察到SIgA水平明显降低。此外，对t细胞应答的详细分析显示，鼻腔BLP-SV疫苗接种促进了Th1/Th17免疫应答，同时增加了iav特异性IgG2c抗体的产生。综上所述，这些结果表明，鼻腔BLP-SV疫苗接种可诱导iav特异性t细胞和b细胞反应，并以tlr2依赖的方式在病毒进入的部位产生系统性和特异性反应。(C) 2014年作者。Elsevier Ltd.出版。
Background: Nasal vaccination is considered to be a promising alternative for parenteral vaccination against influenza virus as it is non-invasive and offers the opportunity to elicit strong antigen-specific responses both systemic and locally at the port of entry of the pathogen. Previous studies showed that non-living bacterium-like particles (BLPs) from the food-grade bacterium Lactococcus lact-is are effective stimulators of local and systemic immune responses when administered intranasally. Moreover, in vitro, BLPs specifically interact with human Toll-like receptor 2 (TLR2), suggestive of a role for TLR2 dependent immune activation by BLPs.Methods: In the present study, we examined the role of TLR2 in vivo in immune activation after nasal administration of BLP mixed with split influenza vaccine (BLP-SV) of influenza A virus (IAV) using TLR2 knockout mice.Results: The systemic Th1 cell and subsequent B-cell responses induced after intranasal BLP-SV vaccination depended on the interaction of BLPs with TLR2. Notably, the BLP-SV-induced class switch to IgG2c depended on the interaction of BLP with TLR2. Local induced IAV-specific Th1 cell responses and the mucosal B-cell responses also depended on interaction of BLP with TLR2. Strongly reduced SIgA levels were observed in TLR2 knockout mice both in the nasal and vaginal lavages. In addition, detailed analysis of the T-cell response revealed that nasal BLP-SV vaccination promoted Th1/Th17 immune responses that coincided with increased IAV-specific IgG2c antibody production.Discussion: Altogether these results indicate that nasal BLP-SV vaccination induces IAV-specific T-cell and B-cell responses, both systemically and at the site of virus entry in a TLR2-dependent manner. (C) 2014 The Authors. Published by Elsevier Ltd.