Nasal delivery of chitosan-DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) induces protective CTL responses in BALB/c mice
Nasal delivery of chitosan-DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) induces protective CTL responses in BALB/c mice
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DOI：
10.1016/s0264-410x(02)00662-x
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发表时间：
2003-03-28
期刊：
影响因子：
5.5
通讯作者：
Illum, L
中科院分区：
文献类型：
--
作者：
Iqbal, M;Lin, W;Illum, L
呼吸道合胞病毒（Respiratory syncytial virus，RSV）是下呼吸道的重要病原体，是新生儿、幼儿和老年人的严重疾病。由于与使用早期开发的疫苗相关的并发症，仍然需要针对RSV的有效疫苗。大多数病原体通过粘膜表面进入体内，因此通过诸如鼻腔的途径递送疫苗可以很好地证明在诱导针对呼吸道病毒的保护性免疫应答方面是上级的，因为鼻腔免疫可以诱导局部和全身免疫。以前，我们已经表明，编码来自RSV M2蛋白的CTL表位的质粒DNA的皮内免疫诱导保护性CTL应答。在本研究中，已研究了用壳聚糖配制的质粒DNA的粘膜递送。壳聚糖是一种多糖，由N-乙酰葡糖胺和葡糖胺的共聚物组成，其衍生自甲壳素，甲壳素是一种存在于甲壳动物壳中的材料。鼻内免疫与质粒DNA与壳聚糖配制诱导肽和病毒特异性CTL反应的BALB/c小鼠，通过皮内免疫诱导的那些。在壳聚糖/DNA免疫小鼠的RSV攻击后，与对照组相比，在免疫小鼠的肺中观察到病毒载量的显著降低（P < 0.001）。这些结果表明了通过鼻内途径用壳聚糖配制的基于表位的疫苗进行免疫的潜力。(C)2002爱思唯尔科技有限公司版权所有。
Respiratory syncytial virus (RSV), an important pathogen of the lower respiratory tract, is responsible for severe illness both in new born and young children and in elderly people. Due to complications associated with the use of the early developed vaccines, there is still a need for an effective vaccine against RSV. Most pathogens enter the body via mucosal surfaces and therefore vaccine delivery via routes such as the nasal, may well prove to be superior in inducing protective immune responses against respiratory viruses, since both local and systemic immunity can be induced by nasal immunisation. Previously we have shown that intradermal immunisation of a plasmid DNA encoding the CTL epitope from the M2 protein of RSV induced protective CTL responses. In the present study, the mucosal delivery of plasmid DNA formulated with chitosan has been investigated. Chitosan is a polysachharide consisting of copolymers of N-acetylglucosamine and glucosamine that is derived from chitin, a material found in the shells of crustacea. Intranasal immunisation with plasmid DNA formulated with chitosan induced peptide- and virus-specific CTL responses in BALB/c mice that were comparable to those induced via intradermal immunisation. Following RSV challenge of chitosan/DNA immunised mice, a significant reduction (P < 0.001) in the virus load was observed in the lungs of immunised mice compared to that in the control group. These results indicate the potential of immunisation with chitosan-formulated epitope-based vaccines via the intranasal route. (C) 2002 Elsevier Science Ltd. All rights reserved.