Westerink M A, Giardina P C
Department of Medicine, State University of New York, Buffalo 14215.
Microb Pathog. 1992 Jan;12(1):19-26. doi: 10.1016/0882-4010(92)90062-s.
We have developed a monoclonal anti-idiotypic antibody, designated 6F9, which acts as the surrogate image of the meningococcal group C capsular polysaccharide (MCP). Murine immunization with 6F9 results in a T-dependent anti-MCP antibody response. To examine the protective nature of the antibody response elicited by 6F9 we performed a series of live challenge studies using a murine model for meningococcal infection in which mice were iron dextran treated and challenged with 10 x LD50 of meningococcal group C strain 35E. Adult BALB/c mice immunized with 6F9 had a 100% survival and a significantly reduced level of bacteremia at 24 h. Mice immunized with MCP had an 80% survival rate, all survivors were bacteremic at 24 h. Neonatal mice primed within 24 h of birth and immunized at 4 weeks of age with 6F9 had a 100% survival and cleared their bacteremia by 8 h, which was significantly faster than the MCP primed and immunized mice. Neonatal mice primed with 6F9 and challenged at 5 weeks of age had a survival rate of 90% which was significantly higher than mice primed with MCP and the control group (60% and 50% survival, respectively). Mice primed at birth and immunized at 8 days had a 100% survival and 90% of these mice had sterile blood cultures by 8 h. Mice primed and immunized with MCP all remained bacteremic at 24 h. These data indicate that the anti-Id 6F9 which mimics the capsular polysaccharide of group C meningococci is capable of inducing protective immunity in immunologically mature as well as immature animals.
我们研制出了一种单克隆抗独特型抗体,命名为6F9,它可作为C群脑膜炎球菌荚膜多糖(MCP)的替代影像。用6F9对小鼠进行免疫会引发依赖T细胞的抗MCP抗体反应。为了检测由6F9引发的抗体反应的保护性,我们使用小鼠脑膜炎球菌感染模型进行了一系列活攻毒研究,在该模型中,小鼠接受右旋糖酐铁处理,并用10倍半数致死量的C群脑膜炎球菌35E菌株进行攻毒。用6F9免疫的成年BALB/c小鼠存活率为100%,且在24小时时菌血症水平显著降低。用MCP免疫的小鼠存活率为80%,所有存活小鼠在24小时时都有菌血症。出生后24小时内进行初免、4周龄时用6F9免疫的新生小鼠存活率为100%,并在8小时内清除了菌血症,这比用MCP初免和免疫的小鼠要快得多。用6F9初免并在5周龄时进行攻毒的新生小鼠存活率为90%,这显著高于用MCP初免的小鼠和对照组(存活率分别为60%和50%)。出生时进行初免、8天时进行免疫的小鼠存活率为100%,其中90%的小鼠在8小时时血培养无菌。用MCP初免和免疫的小鼠在24小时时都仍有菌血症。这些数据表明,模拟C群脑膜炎球菌荚膜多糖的抗独特型抗体6F9能够在免疫成熟和未成熟的动物中诱导保护性免疫。