Corthésy Blaise, Boris Soledad, Isler Patrick, Grangette Corinne, Mercenier Annick
R and D Laboratory of the Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
J Infect Dis. 2005 Oct 15;192(8):1441-9. doi: 10.1086/444425. Epub 2005 Sep 13.
The development of an efficacious vaccine against infection with Helicobacter pylori, the causative agent of chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma, remains a challenge. Since the use of mucosal adjuvants is limited in human application, we have evaluated the potential of recombinant Lactobacillus strains producing H. pylori urease B (UreB) subunit to deliver this antigen to the gastrointestinal tract.
Mice were injected orally 3 times with a triple dose of recombinant Lactobacillus plantarum NCIMB8826, the recombinant isogenic cell-wall mutant (alr(-) MD007 strain) expressing UreB, or a mixture of recombinant UreB and cholera toxin (rUreB/CT) as a control. Urease-specific seric immunoglobulin (Ig) G and IgA were measured by use of an enzyme-linked immunosorbent assay. After challenge with Helicobacter felis, stomach infection was examined by use of the rapid urease test and by polymerase chain reaction detection of Helicobacter genomic DNA.
Intragastric immunization with both recombinant Lactobacillus strains and rUreB/CT elicited UreB-specific antibodies. After challenge, reduction of H. felis load in the stomachs of mice was observed only after immunization with the recombinant mutant strain MD007 or with rUreB/CT.
This is the first report of successful induction of partial protection against H. felis with a mucosal prime-boost regimen in which recombinant Lactobacillus strains were used as antigen-delivery vehicles.
开发一种有效的疫苗来预防幽门螺杆菌感染仍然是一项挑战，幽门螺杆菌是慢性胃炎、消化性溃疡病和胃腺癌的病原体。由于黏膜佐剂在人体应用中受到限制，我们评估了产生幽门螺杆菌尿素酶B（UreB）亚基的重组乳酸杆菌菌株将该抗原递送至胃肠道的潜力。
给小鼠口服注射3次重组植物乳杆菌NCIMB8826、表达UreB的重组同基因细胞壁突变体（alr(-) MD007菌株）或重组UreB与霍乱毒素的混合物（rUreB/CT）作为对照，剂量为三倍。使用酶联免疫吸附测定法测量尿素酶特异性血清免疫球蛋白（Ig）G和IgA。在用猫幽门螺杆菌攻击后，通过快速尿素酶试验和聚合酶链反应检测幽门螺杆菌基因组DNA来检查胃部感染情况。
用重组乳酸杆菌菌株和rUreB/CT进行胃内免疫均引发了UreB特异性抗体。攻击后，仅在用重组突变菌株MD007或rUreB/CT免疫后，观察到小鼠胃中猫幽门螺杆菌载量降低。
这是首次报道使用重组乳酸杆菌菌株作为抗原递送载体的黏膜初免 - 加强方案成功诱导对猫幽门螺杆菌的部分保护。
