Van den Broeck W, Cox E, Goddeeris B M
Laboratory of Veterinary Immunology, Faculty of Veterinary Medicine, Universiteit Gent, Merelbeke, Belgium.
Vaccine. 1999 Apr 9;17(15-16):2020-9. doi: 10.1016/s0264-410x(98)00406-x.
An effective way of stimulating the mucosal immune system was examined in piglets, using F4 fimbriae of enterotoxigenic Escherichia coli (ETEC). It was demonstrated that purified F4 fimbriae, as opposed to ovalbumin (OVA), are powerful oral immunogens. Indeed, oral administration of purified F4 induced antigen-specific antibody-secreting cells (ASC) in the Peyer's patches, mesenteric lymph nodes (LN), blood and lamina propria 4, 7, 9 and 11 days postimmunization, respectively, indicating a stimulation of the mucosal immune system, whereas upon oral administration of OVA, no immune response was observed. Moreover, the induced F4-specific IgA and IgG antibody responses were comparable with those obtained upon oral infection with viable E. coli and intramuscular (i.m.) F4 injection, respectively. Furthermore, a priming of the mucosal immune system is better obtained by oral infection (ASC localized in mesenteric LN) than by i.m. F4 injection (ASC localized in spleen and retropharyngeal LN) since an oral boost with purified F4 induced a secondary response in the orally infected animal (mainly IgA and IgG ASC, rapid increase of IgA antibodies) while in the i.m. primed animal a secondary (more circulating antigen-specific ASC than in the unprimed animal) as well as a primary IgM and IgA response (mainly IgM ASC, slow increase of IgA antibodies), suggesting a primary mucosal response, were seen. An oral challenge of the naive control displayed a primary response (mainly IgM ASC, slow increase of IgA and IgG antibodies). The capacity of purified F4 to activate the mucosal immune system on oral administration, is of importance for the development of oral vaccines against ETEC infections.
利用产肠毒素大肠杆菌（ETEC）的F4菌毛，在仔猪中研究了一种刺激黏膜免疫系统的有效方法。结果表明，与卵清蛋白（OVA）不同，纯化的F4菌毛是强大的口服免疫原。事实上，口服纯化的F4分别在免疫后4、7、9和11天在派尔集合淋巴结、肠系膜淋巴结（LN）、血液和固有层中诱导出抗原特异性抗体分泌细胞（ASC），表明黏膜免疫系统受到刺激，而口服OVA时未观察到免疫反应。此外，诱导的F4特异性IgA和IgG抗体反应分别与口服活大肠杆菌感染和肌肉注射（i.m.）F4后获得的反应相当。此外，通过口服感染（ASC定位于肠系膜LN）比通过i.m. F4注射（ASC定位于脾脏和咽后LN）能更好地启动黏膜免疫系统，因为用纯化的F4进行口服加强免疫在口服感染的动物中诱导了二次反应（主要是IgA和IgG ASC，IgA抗体迅速增加），而在i.m. 启动的动物中则出现了二次反应（循环中的抗原特异性ASC比未启动的动物更多）以及初次IgM和IgA反应（主要是IgM ASC，IgA抗体缓慢增加），提示出现了初次黏膜反应。对未接触过抗原的对照进行口服攻击显示出初次反应（主要是IgM ASC，IgA和IgG抗体缓慢增加）。纯化的F4口服给药时激活黏膜免疫系统的能力对于开发针对ETEC感染的口服疫苗具有重要意义。
