Intranasal immunization with genetically detoxified diphtheria toxin induces T cell responses in humans: enhancement of Th2 responses and toxin-neutralizing antibodies by formulation with chitosan
Intranasal immunization with genetically detoxified diphtheria toxin induces T cell responses in humans: enhancement of Th2 responses and toxin-neutralizing antibodies by formulation with chitosan
复制标题
DOI：
10.1016/j.vaccine.2003.09.012
复制
发表时间：
2004-02-25
期刊：
影响因子：
5.5
通讯作者：
Mills, KHG
中科院分区：
文献类型：
--
作者：
McNeela, EA;Jabbal-Gill, I;Mills, KHG
我们以前报道过，用白喉毒素的无毒突变交叉反应材料(CRM)(197)经鼻免疫，用壳聚糖配制，在小鼠和豚鼠中产生保护性中和抗体。此外，我们还证明了以CRM197为基础的疫苗粉剂鼻腔给药耐受性良好，显著增强了成年志愿者的抗体反应。在此，我们报道了CRM197单独或与壳聚糖鼻内加强免疫可诱导系统T细胞反应。我们首次提出在人类鼻腔接种疫苗后T细胞亚型的诱导。与传统白喉类毒素疫苗的非肠道免疫一样，鼻腔接种CRM197可增强抗原特异性干扰素-γ的产生。然而，含有壳聚糖的鼻腔白喉疫苗的配方显著增强了Th2型应答，这与经鼻免疫的个体的毒素中和抗体的保护水平有关。这些结果表明，能够诱导强烈Th2型反应的疫苗，如用壳聚糖配制的CRM197，有可能开发出一种针对人类白喉的保护性黏膜疫苗。此外，我们的发现表明，具有适当递送系统的粘膜亚单位疫苗在加强成人免疫方面具有相当大的潜力。(C)2003爱思唯尔有限公司。保留所有权利。
We previously reported that intranasal immunization with a non-toxic mutant cross-reacting material (CRM)(197) of diphtheria toxin, formulated with chitosan, generated protective neutralizing antibodies in mice and guinea pigs. Furthermore, we demonstrated that intranasal delivery of a powder formulation of the CRM197-based vaccine was well tolerated and significantly boosted antibody responses in adult volunteers. Here we report that intranasal booster immunization with CRM197 alone or with chitosan induced systemic T cell responses. We addressed for the first time the induction of T cell subtypes following intranasal vaccination in humans. Intranasal vaccination with CRM197, like parenteral immunization with a conventional diphtheria toxoid vaccine, enhanced antigen-specific IFN-gamma production. However, formulation of the nasal diphtheria vaccine with chitosan significantly augmented Th2-type responses, which correlated with protective levels of toxin-neutralizing antibodies in intranasally boosted individuals. The results suggest that vaccines capable of inducing strong Th2-type responses, such as CRM197 formulated with chitosan, have potential for the development of a protective mucosal vaccine against diphtheria in humans. Furthermore, our findings demonstrate that mucosal subunit vaccines with appropriate delivery systems have considerable potential for booster immunization of adults. (C) 2003 Elsevier Ltd. All rights reserved.