Foss D L, Murtaugh M P
University of Minnesota, Department of Veterinary PathoBiology, St. Paul 55108, USA.
Vaccine. 1999 Feb 26;17(7-8):788-801. doi: 10.1016/s0264-410x(98)00263-1.
The oral immunogenic and adjuvant properties of cholera toxin (CT) and its nontoxic B subunit (CT-B) were assessed in swine. Both whole CT and CT-B are oral immunogens in swine and CT is relatively more potent. Oral administration of 100 microg of CT resulted in a greater immune response than 1 mg of CT-B as measured by anti-CT-B IgA, IgG and IgM in local (jejunum) and distant (oral cavity) mucosal sites, and in systemic sites including blood and spleen. Lower doses of CT were potent adjuvants for the response to CT-B, but did not induce detectable immunity alone. The predominant response to oral CT-B administered with CT was intestinally produced and secreted IgA, with about 2500 per 10(6) jejunal lamina propria cells producing anti-CT-B IgA in immunized animals. While CT is a potent adjuvant for CT-B, its ability to act as adjuvant for heterologous proteins is more restricted. 50 microg of CT in combination with 1 mg of CT-B did not induce antibodies to 25 mg of coadministered KLH. However, chemical linking of ovalbumin to CT-B and coadministration with CT resulted in a detectable antibody response to ovalbumin. These results suggest that CT is immunogenic and is a potent adjuvant for CT-B in swine and that the induction of mucosal immunity to heterologous antigens may require specific targeting to the gut-associated lymphoid tissues.
在猪身上评估了霍乱毒素(CT)及其无毒B亚基(CT-B)的口服免疫原性和佐剂特性。完整的CT和CT-B在猪体内都是口服免疫原,且CT的效力相对更强。口服100微克CT所引发的免疫反应比1毫克CT-B更强,这一结果通过局部(空肠)和远端(口腔)黏膜部位以及包括血液和脾脏在内的全身部位的抗CT-B IgA、IgG和IgM来衡量。较低剂量的CT是CT-B免疫反应的有效佐剂,但单独使用时不会诱导出可检测到的免疫力。与CT联合口服的CT-B所引发的主要反应是肠道产生并分泌IgA,在免疫动物中,每10^6个空肠固有层细胞中约有2500个产生抗CT-B IgA。虽然CT是CT-B的有效佐剂,但其作为异源蛋白佐剂的能力更为有限。50微克CT与1毫克CT-B联合使用时,不会诱导产生针对25毫克同时给予的钥孔戚血蓝蛋白(KLH)的抗体。然而,将卵清蛋白与CT-B化学连接并与CT联合给药,会引发对卵清蛋白的可检测到的抗体反应。这些结果表明,CT具有免疫原性,是猪体内CT-B的有效佐剂,并且对异源抗原诱导黏膜免疫可能需要特异性靶向肠道相关淋巴组织。