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重组蛋白G1F/M2诱导小鼠产生的针对呼吸道合胞病毒的持久平衡免疫和保护效力

Long-lasting balanced immunity and protective efficacy against respiratory syncytial virus in mice induced by a recombinant protein G1F/M2.

作者信息

Zeng Ruihong, Qi Xiaowen, Gong Wei, Mei Xingguo, Wei Lin, Ma Cuiqing, Yin Xiaolin

机构信息

Department of Immunology, Hebei Medical University, Shijiazhuang 050017, China.

出版信息

Vaccine. 2007 Oct 16;25(42):7422-8. doi: 10.1016/j.vaccine.2007.08.007. Epub 2007 Aug 23.

DOI:10.1016/j.vaccine.2007.08.007
PMID:17850930
Abstract

Respiratory syncytial virus (RSV) is the primary cause of serious lower respiratory tract illness in young children. We have engineered a recombinant candidate vaccine G1F/M2, consisting of a cytotoxic T lymphocyte (CTL) epitope of RSV-M2 protein and a domain of RSV-G protein. In this study, the long-term immunogenicity and protective effect were evaluated. In G1F/M2-immunized mice, special antibodies lasted for more than 19 weeks, and the IgG1/IgG2a ratio remained a balanced level till the end of the study, suggesting mixed Th1/Th2 type of responses. Concomitantly, G1F/M2 elicited long-lived RSV-specific CTL activity that was detectable at 12 weeks after the final immunization. Stronger CTL responses were induced with immunization once more at 13 weeks after the last immunization in G1F/M2-primed mice than those in F/M2-primed mice. These results suggest that G1F/M2-induced long-lasting balanced humoral and cellular immunity responses, and immunological memory in mice. Furthermore, following RSV challenge, long-term protective efficacy was observed. RSV replication in lungs of G1F/M2-primed mice elicited also mixed Th1/Th2 responses, a property that is considered advantageous for the safety of an RSV vaccine. Therefore, G1F/M2 is a promising RSV subunit vaccine.

摘要

呼吸道合胞病毒(RSV)是幼儿严重下呼吸道疾病的主要病因。我们构建了一种重组候选疫苗G1F/M2,它由RSV-M2蛋白的细胞毒性T淋巴细胞(CTL)表位和RSV-G蛋白的一个结构域组成。在本研究中,评估了其长期免疫原性和保护作用。在接种G1F/M2的小鼠中,特异性抗体持续了超过19周,并且IgG1/IgG2a比值直至研究结束都保持在平衡水平,提示Th1/Th2混合型反应。同时,G1F/M2引发了持久的RSV特异性CTL活性,在末次免疫后12周仍可检测到。在G1F/M2初免的小鼠中,末次免疫后13周再次免疫诱导的CTL反应比F/M2初免的小鼠更强。这些结果表明,G1F/M2在小鼠中诱导了持久的平衡体液免疫和细胞免疫反应以及免疫记忆。此外,在RSV攻击后,观察到了长期保护效果。G1F/M2初免小鼠肺部的RSV复制也引发了Th1/Th2混合型反应,这一特性被认为对RSV疫苗的安全性有利。因此,G1F/M2是一种有前景的RSV亚单位疫苗。

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引用本文的文献

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Simultaneous Administration of Recombinant Measles Viruses Expressing Respiratory Syncytial Virus Fusion (F) and Nucleo (N) Proteins Induced Humoral and Cellular Immune Responses in Cotton Rats.同时接种表达呼吸道合胞病毒融合(F)蛋白和核(N)蛋白的重组麻疹病毒可在棉鼠体内诱导体液免疫和细胞免疫反应。
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