不同疫苗递送系统诱导小鼠抗结核保护作用的比较。

Comparison of different delivery systems of vaccination for the induction of protection against tuberculosis in mice.

作者信息

Lima K M, Bonato V L, Faccioli L H, Brandão I T, dos Santos S A, Coelho-Castelo A A, Leão S C, Silva C L

机构信息

Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, 14049-900, SP, Ribeirao Preto, Brazil.

出版信息

Vaccine. 2001 May 14;19(25-26):3518-25. doi: 10.1016/s0264-410x(01)00042-1.

DOI:10.1016/s0264-410x(01)00042-1

PMID:11348719

Abstract

The way to deliver antigens and cellular requirements for long-lasting protection against tuberculosis are not known. Immunizations with mycobacterial 65 kDa heat shock protein (hsp65) expressed from J774-hsp65 cells (antigen-presenting cells that endogenously produce hsp65 antigen) or from plasmid DNA, or with the protein entrapped in cationic liposomes, can each give protective immunity similar to that obtained from live Bacillus Calmette Guérin (BCG), whereas injecting the protein in Freund's incomplete adjuvant (FIA) has minimal effect. Protective procedures elicited high frequencies of antigen-reactive alphabeta T cells with CD4+/CD8- and CD8+/CD4- phenotypes. Protection correlated with the abundance of hsp65-dependent cytotoxic CD8+/CD4-/CD44hi cells. The frequency of these cells and the level of protection declined during 8 months after J774-hsp65 or liposome-mediated immunization with hsp65 protein but were sustained or steadily increased over this period after hsp65-DNA or BCG immunizations. IFN-gamma predominated over IL-4 among the hsp65-reactive CD8+/CD4- and CD4+/CD8- populations after J774-hsp65-, hsp65-liposome-, and hsp65-DNA-mediated immunizations, but similar levels of these cytokines prevailed after BCG vaccination.

摘要

目前尚不清楚提供抗原和细胞需求以实现针对结核病的长期保护的方法。用J774-hsp65细胞（内源性产生hsp65抗原的抗原呈递细胞）或质粒DNA表达的分枝杆菌65 kDa热休克蛋白（hsp65）进行免疫，或用包裹在阳离子脂质体中的蛋白质进行免疫，每种方法都能产生与活卡介苗（BCG）相似的保护性免疫，而在弗氏不完全佐剂（FIA）中注射该蛋白质的效果则微乎其微。保护性程序引发了高频率的具有CD4+/CD8-和CD8+/CD4-表型的抗原反应性αβ T细胞。保护作用与hsp65依赖性细胞毒性CD8+/CD4-/CD44hi细胞的丰度相关。在用J774-hsp65或脂质体介导的hsp65蛋白免疫后的8个月内，这些细胞的频率和保护水平下降，但在hsp65-DNA或BCG免疫后的这段时间内保持稳定或稳步增加。在J774-hsp65、hsp65-脂质体和hsp65-DNA介导的免疫后，hsp65反应性CD8+/CD4-和CD4+/CD8-群体中IFN-γ的含量超过IL-4，但在BCG疫苗接种后，这些细胞因子保持相似水平。