Protection against bubonic and pneumonic plague with a single dose microencapsulated sub-unit vaccine

Protection against bubonic and pneumonic plague with a single dose microencapsulated sub-unit vaccine
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DOI:
10.1016/j.vaccine.2005.12.016
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发表时间:
2006-05-15
期刊:
影响因子:
5.5
通讯作者:
Williamson, ED
Williamson, ED
中科院分区:
医学3区
文献类型:
--
作者:
Elvin, SJ;Eyles, JE;Williamson, ED

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通过在BALB/c小鼠中单次施用来自鼠疫耶尔森氏菌的微囊化Caf 1和LcrV抗原,提供了对通过胃肠外和气溶胶途径的强毒鼠疫攻击的保护。重组Caf 1和LcrV分别封装在聚合物微球中,其表面吸附了额外的抗原。将含有Caf 1或LcrV的微球混合,并通过鼻内或肌内途径一次性免疫小鼠。两种途径的免疫接种诱导全身和局部免疫应答,与高水平的血清IgG正在开发的两种疫苗抗原的反应。在Elispot测定中,证实了脾和引流淋巴结细胞分泌细胞因子,揭示了Th 1和Th 2相关细胞因子的活化;并且发现通过任一途径免疫的动物的脾细胞在体外响应于两种疫苗抗原而增殖。毒力攻击实验表明,通过鼻内滴注的非侵入性免疫可以提供强的全身和局部免疫应答,并保护免受高水平攻击。这些疫苗抗原的微囊化具有额外的优点,即抗原的受控释放在体内发生,使得仅在单次免疫剂量后就可以诱导保护性免疫。(c)2005年皇冠版权Dstl。由爱思唯尔有限公司出版。保留所有权利。
Protection against virulent plague challenge by the parenteral and aerosol routes was afforded by a single administration of microencapsulated Caf1 and LcrV antigens from Yersinia pestis in BALB/c mice. Recombinant Caf1 and LcrV were individually encapsulated in polymeric microspheres, to the surface of which additional antigen was adsorbed. The microspheres containing either Caf1 or LcrV were blended and used to immunise mice on a single occasion, by either the intra-nasal or intra-muscular route. Both routes of immunisation induced systemic and local immune responses, with high levels of serum IgG being developed in response to both vaccine antigens. In Elispot assays, secretion of cytokines by spleen and draining lymph node cells was demonstrated, revealing activation of both Th1 and Th2 associated cytokines; and spleen cells from animals immunised by either route were found to proliferate in vitro in response to both vaccine antigens. Virulent challenge experiments demonstrated that non-invasive immunisation by intra-nasal instillation can provide strong systemic and local immune responses and protect against high level challenge. Microencapsulation of these vaccine antigens has the added advantage that controlled release of the antigens occurs in vivo, so that protective immunity can be induced after only a single immunising dose. (c) 2005 Crown Copyright Dstl. Published by Elsevier Ltd. All rights reserved.