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口服痘苗病毒重组体后诱导的黏膜和全身免疫反应。

Mucosal and systemic immune responses induced after oral delivery of vaccinia virus recombinants.

作者信息

Gherardi M M, Esteban M

机构信息

Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autónoma, Madrid, Spain.

出版信息

Vaccine. 1999 Mar 5;17(9-10):1074-83. doi: 10.1016/s0264-410x(98)00324-7.

Abstract

The immune responses elicited after oral delivery of vaccinia virus (VV) recombinants are not well defined. In this study we show with mice, that after oral administration of a VV recombinant expressing the luciferase reporter gene, VV gene expression takes place for several days in gut-associated lymphoid (GALT) tissues as well as in the spleen. After 14 days, a significant mucosal IgA response against VV was detected in vaginal and intestinal washings, as well as a systemic specific IgG response, which was principally of the IgG2a subclass. Furthermore, orally immunized mice developed cellular immune responses to VV (CD8+ T cells and T helper activities) in mesenteric lymph nodes (MLN) and spleen. Oral immunization with a VV recombinant expressing, either the envelope protein of HIV or beta-galactosidase, induced a specific immune response, locally and systemically, against gp120 and beta-gal. The cytokine pattern found in supernatants of spleen and MLN cells after stimulation with VV antigens or gp120 was clearly of type 1 cytokines. These studies demonstrate that VV recombinants administered by the oral route generate mucosal and systemic immune responses against antigens of the virus vector and to the recombinant products. These observations are of significance in the use of poxvirus vectors as vaccines.

摘要

口服痘苗病毒(VV)重组体后引发的免疫反应尚未得到充分阐明。在本研究中,我们以小鼠为实验对象,发现口服表达荧光素酶报告基因的VV重组体后,VV基因在肠道相关淋巴组织(GALT)以及脾脏中持续表达数天。14天后,在阴道和肠道灌洗液中检测到针对VV的显著黏膜IgA反应,以及全身性特异性IgG反应,主要为IgG2a亚类。此外,经口服免疫的小鼠在肠系膜淋巴结(MLN)和脾脏中对VV产生了细胞免疫反应(CD8 + T细胞和T辅助活性)。口服表达HIV包膜蛋白或β - 半乳糖苷酶的VV重组体可诱导针对gp120和β - gal的局部和全身性特异性免疫反应。用VV抗原或gp120刺激后,在脾脏和MLN细胞上清液中发现的细胞因子模式明显属于1型细胞因子。这些研究表明,经口服途径给予的VV重组体可产生针对病毒载体抗原和重组产物的黏膜和全身性免疫反应。这些观察结果对于痘苗病毒载体作为疫苗的应用具有重要意义。

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