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用铝非吸附白喉类毒素与重组霍乱毒素B亚单位作为佐剂经鼻内免疫小鼠后诱导全身和黏膜抗体反应。

Induction of systemic and mucosal antibody responses in mice immunized intranasally with aluminium-non-adsorbed diphtheria toxoid together with recombinant cholera toxin B subunit as an adjuvant.

作者信息

Isaka M, Yasuda Y, Kozuka S, Taniguchi T, Matano K, Maeyama J, Komiya T, Ohkuma K, Goto N, Tochikubo K

机构信息

Department of Microbiology, Nagoya City University Medical School, Mizuho-ku, Nagoya, Japan.

出版信息

Vaccine. 1999 Nov 12;18(7-8):743-51. doi: 10.1016/s0264-410x(99)00258-3.

DOI:10.1016/s0264-410x(99)00258-3
PMID:10547435
Abstract

Nasal mucosal immunization is very attractive for vaccination to prevent various bacterial and viral infectious diseases because of induction of systemic and mucosal immune responses. The aim of the present study was to investigate the possibility of changing the immunization procedure of diphtheria toxoid (DT) from intramuscular or subcutaneous injection to intranasal administration. Intranasal immunization with aluminium-non-adsorbed diphtheria toxoid (nDT) together with recombinant cholera toxin B subunit (rCTB, 10 microg) induced, at a concentration of 5 Lf, high levels of serum DT-specific IgG antibody responses and high or moderate levels of the specific IgA antibody responses in all mice and only a slight level of the specific IgE antibody responses in some mice. Furthermore, sufficiently high diphtheria antitoxin titres more than 0.1 international units (IU) ml(-1) were obtained from mice which showed high levels of serum DT-specific IgG antibody responses. Under the same experimental conditions, induction of significant levels of mucosal DT-specific IgA antibody responses occurred in the nasal cavity, the lung, the saliva and vaginal secretions and the small and large intestines of all mice, although there were different titres between individual mice. Similar results were also obtained with rCTB-specific serum IgG and IgA and mucosal IgA antibody responses; serum rCTB-specific IgE antibody titres were not detected. These results show that intranasal administration of nDT with rCTB must be a very useful means for vaccination against diphtheria.

摘要

由于能诱导全身和黏膜免疫反应,鼻黏膜免疫在预防各种细菌和病毒感染性疾病的疫苗接种方面极具吸引力。本研究的目的是探讨将白喉类毒素(DT)的免疫接种程序从肌肉注射或皮下注射改为鼻内给药的可能性。用未吸附铝的白喉类毒素(nDT)与重组霍乱毒素B亚单位(rCTB,10微克)进行鼻内免疫,在浓度为5Lf时,所有小鼠均诱导出高水平的血清DT特异性IgG抗体反应以及高或中等水平的特异性IgA抗体反应,部分小鼠仅出现轻微水平的特异性IgE抗体反应。此外,从血清DT特异性IgG抗体反应水平高的小鼠中获得了足够高的白喉抗毒素滴度,超过0.1国际单位(IU)/毫升。在相同实验条件下,所有小鼠的鼻腔、肺部、唾液和阴道分泌物以及小肠和大肠均诱导出显著水平的黏膜DT特异性IgA抗体反应,尽管个体小鼠之间的滴度有所不同。rCTB特异性血清IgG和IgA以及黏膜IgA抗体反应也得到了类似结果;未检测到血清rCTB特异性IgE抗体滴度。这些结果表明,nDT与rCTB鼻内给药必定是预防白喉疫苗接种的一种非常有用的方法。

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