Experimental intracerebral vaccination protects mouse from a neurotropic virus by attracting antibody secreting cells to the CNS
Experimental intracerebral vaccination protects mouse from a neurotropic virus by attracting antibody secreting cells to the CNS
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DOI：
10.1016/j.imlet.2011.05.008
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发表时间：
2011-09-30
影响因子：
4.4
通讯作者：
Umemura, Takashi
中科院分区：
文献类型：
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作者：
Lee, Hyunkyoung;Sunden, Yuji;Umemura, Takashi
在先前的研究中，我们发现脑内（IC）免疫小鼠的脑脊液中有抗原特异性抗体（Abs），并且可以在致死剂量的经神经传播病毒中存活。为了更好地了解这背后的机制，中枢神经系统（CNS）和淋巴器官的免疫反应后，脑内免疫伪狂犬病病毒（PRV）的研究，重点是抗体分泌细胞（ASC）。IC免疫的小鼠具有比SC免疫的小鼠显著更高的PRV特异性血清Abs和中和Abs滴度。IC免疫小鼠脾和颈淋巴结（CLN）产生的PRV特异性抗体显著高于SC免疫小鼠。IC免疫小鼠脑中主要检测到ASC、免疫球蛋白和IgG、CXCL9、10、13和BAFF的mRNA，而SC免疫小鼠脑中未检测到ASC、免疫球蛋白和IgG、CXCL9、10、13和BAFF的mRNA。当PRV直接接种到脑中时，IC免疫的小鼠（86%）比皮下（SC）免疫的小鼠（33%）通过抑制病毒繁殖而存活。总之，IC免疫诱导更有效的免疫应答，以保护中枢神经系统免受PRV感染，通过吸引ASC进入中枢神经系统，并诱导更多的PRV特异性血清中和抗体。这种方法可能具有重要的意义，作为一种新的治疗程序，在人类和动物的嗜神经病毒感染。(C)2011 Elsevier B.V.保留所有权利。
In previous studies, we showed that intracerebrally (IC) immunized mice had antigen-specific antibodies (Abs) in cerebrospinal fluid and could survive lethal doses of transneurally spreading viruses. To better understand the mechanisms behind this, immune responses in both the central nervous system (CNS) and lymphoid organs following intracerebral immunization against pseudorabies virus (PRV) were investigated by focusing on antibody secreting cells (ASCs). IC immunized mice had significantly higher PRV-specific serum Abs and neutralizing Abs titers than SC immunized mice. Spleen and cervical lymph nodes (CLNs) of IC immunized mice produced significantly more PRV-specific Abs than that of SC immunized mice. ASCs, immunoglobulin and mRNAs of IgG, CXCL9, 10, 13 and BAFF were predominantly detected in the brain of IC immunized mice, but not in SC immunized mice. IC immunized mice (86%) survived more than subcutaneously (SC) immunized mice (33%) by suppression of virus propagation, when PRV was inoculated directly into the brain. In conclusion, IC immunization induced more effective immune responses to protect the CNS from PRV infection by attracting ASCs into the CNS and inducing much more PRV-specific serum neutralizing Abs. This approach may have important implications as a novel treatment procedure for neurotropic virus infections in both humans and animals. (C) 2011 Elsevier B.V. All rights reserved.