Quiding-Järbrink M, Lönroth H, Ahlstedt I, Holmgren J, Svennerholm A M
Department of Medical Microbiology and Immunology, Göteborg University, Göteborg, Sweden.
Gut. 2001 Oct;49(4):512-8. doi: 10.1136/gut.49.4.512.
In a previous study, we found that oral vaccination induces strong B cell responses in the stomach of Helicobacter pylori infected but not of uninfected individuals. In this study, we have evaluated the possibility of inducing gastric immune responses in H pylori infected volunteers by intestinal and gastric immunisation.
H pylori infected subjects were given two doses of an inactivated cholera vaccine, either intestinally via an endoscope approximately 30 cm distal to the pylorus sphincter or intragastrically as small droplets applied directly onto the stomach mucosa. Uninfected individuals received the vaccine by standard oral procedure. Vaccine specific antibody secreting cells in antral and duodenal biopsies were detected by the enzyme linked immunospot assay technique before and seven days after the second immunisation.
Intestinal immunisations resulted in induction of vaccine specific gastric IgA secreting cells in five of eight volunteers. This immunisation schedule also gave rise to specific duodenal antibody secreting cells in seven of eight individuals. Local gastric immunisation resulted in the induction of specific B cells in the gastric mucosa of four of eight volunteers. Gastric antigen application also resulted in B cell responses in the duodenum in all volunteers. Uninfected volunteers receiving the vaccine perorally responded in the duodenum but not in the stomach.
H pylori infection increases the ability of the gastric mucosa to serve as an expression site for intestinally induced B cell responses. These findings are of importance when designing a therapeutic H pylori vaccine, and based on our results such a vaccine can be delivered along the whole upper gastrointestinal tract.
在之前的一项研究中,我们发现口服疫苗在幽门螺杆菌感染个体的胃中可诱导强烈的B细胞反应,但在未感染个体中则不然。在本研究中,我们评估了通过肠道和胃部免疫在幽门螺杆菌感染的志愿者中诱导胃部免疫反应的可能性。
幽门螺杆菌感染的受试者接受两剂灭活霍乱疫苗,要么通过内镜在距幽门括约肌约30厘米处经肠道接种,要么以小滴形式直接滴在胃黏膜上进行胃内接种。未感染个体通过标准口服程序接种疫苗。在第二次免疫前和免疫后7天,通过酶联免疫斑点分析技术检测胃窦和十二指肠活检组织中分泌疫苗特异性抗体的细胞。
肠道免疫在8名志愿者中的5名中诱导出了分泌疫苗特异性胃IgA的细胞。这种免疫方案在8名个体中的7名中还产生了特异性十二指肠抗体分泌细胞。局部胃免疫在8名志愿者中的4名的胃黏膜中诱导出了特异性B细胞。胃内接种抗原也在所有志愿者的十二指肠中引发了B细胞反应。经口接种疫苗的未感染志愿者在十二指肠中有反应,但在胃中无反应。
幽门螺杆菌感染增加了胃黏膜作为肠道诱导的B细胞反应表达部位的能力。这些发现对于设计治疗性幽门螺杆菌疫苗具有重要意义,基于我们的结果,这样的疫苗可以沿整个上消化道递送。