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当与大肠杆菌不耐热肠毒素经鼻共同给药时,裸露的DNA能有效地引发针对编码抗原的全身性B细胞和T细胞反应。

Naked DNA when co-administered intranasally with heat-labile enterotoxin of Escherichia coli primes effectively for systemic B- and T-cell responses to the encoded antigen.

作者信息

Kanellos T S, Byarugaba D K, Russell P H, Howard C R, Partidos C D

机构信息

Department of Pathology and Infectious Diseases, The Royal Veterinary College, Royal College Street, NW I OTU, London, UK.

出版信息

Immunol Lett. 2000 Nov 1;74(3):215-20. doi: 10.1016/s0165-2478(00)00257-1.

DOI:10.1016/s0165-2478(00)00257-1
PMID:11064104
Abstract

In this study a novel prime-boost immunisation strategy was evaluated. Priming of BALB/c mice by the intranasal route with plasmid DNA encoding beta-galactosidase (LacZ) with or without heat-labile enterotoxin (LT) of Escherichia coli as a mucosal adjuvant, resulted in the induction of weak serum antibody and proliferative T-cell responses. However, following an intraperitoneal booster injection with the beta-galactosidase protein (beta-gal), strong antibody and proliferative T-cell responses were induced in all the mice. These responses were highest in mice primed intranasally with a mixture of LacZ+LT as compared to those mice primed with DNA (LacZ) or protein (beta-gal) alone. Moreover, LacZ+LT primed mice produced high avidity antibodies and the subclasses of serum antibodies were IgG1 and IgG2a, suggesting a mixed Th1/Th2-type response. Priming of mice with either protein (beta-gal) or DNA (LacZ) alone, produced predominantly IgG1 antibodies, suggesting a Th2-type response. These findings suggest that the use of a heterologous DNA-prime, protein-boost immunisation scheme combining different routes of administration, might be an advantageous strategy for the induction of accelerated immune responses.

摘要

在本研究中,对一种新型的初免-加强免疫策略进行了评估。通过鼻内途径用编码β-半乳糖苷酶(LacZ)的质粒DNA对BALB/c小鼠进行初免,同时或不同时添加大肠杆菌不耐热肠毒素(LT)作为黏膜佐剂,结果诱导出较弱的血清抗体和增殖性T细胞反应。然而,在用β-半乳糖苷酶蛋白(β-gal)进行腹腔加强注射后,所有小鼠均诱导出强烈的抗体和增殖性T细胞反应。与单独用DNA(LacZ)或蛋白(β-gal)进行初免的小鼠相比,用LacZ+LT混合物进行鼻内初免的小鼠的这些反应最为强烈。此外,LacZ+LT初免的小鼠产生了高亲和力抗体,血清抗体亚类为IgG1和IgG2a,表明是一种混合的Th1/Th2型反应。单独用蛋白(β-gal)或DNA(LacZ)对小鼠进行初免,主要产生IgG1抗体,表明是一种Th2型反应。这些发现表明,使用结合不同给药途径的异源DNA初免、蛋白加强免疫方案,可能是诱导加速免疫反应的一种有利策略。

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