Age-related disparity in functional activities of human group C serum anticapsular antibodies elicited by meningococcal polysaccharide vaccine
Age-related disparity in functional activities of human group C serum anticapsular antibodies elicited by meningococcal polysaccharide vaccine
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DOI：
10.1128/iai.71.1.275-286.2003
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发表时间：
2003-01-01
影响因子：
3.1
通讯作者：
Granoff, DA
中科院分区：
文献类型：
--
作者：
Harris, SL;King, WJ;Granoff, DA
血清杀菌活性赋予对脑膜炎球菌病的保护作用，但尚不清楚缺乏杀菌活性的疫苗诱导的抗荚膜抗体是否具有保护作用。我们开发了一个婴儿大鼠的挑战模型，使用自然发生的O-乙酰化菌株的脑膜炎奈瑟菌C组和一个菌株，是阴性的O乙酰化（醋酸乙酯）。将4至7日龄的大鼠腹膜内（i. p.）18小时后，两种菌株的菌落数均接近10（3）CFU，血液中的菌落数均大于5 × 10（5）CFU/ml。在细菌攻击前2小时腹膜内注射免疫前血清的稀释液对菌血症没有影响，而在用脑膜炎球菌多糖疫苗免疫的成人血清中的C组抗囊抗体在低至0.04 μ g/大鼠的抗体剂量下分别赋予针对OAc阳性或OAc阴性菌株的完全或部分保护（每毫升血液中CFU减少>99%）。在平均年龄为2.6岁的免疫儿童的合并血清中，抗囊抗体的剂量高5倍（0.18至0.2 μ g/大鼠）未能保护大鼠，但在4岁免疫儿童的血清池中，相同或低5倍剂量的抗体提供了完全或部分保护。用缺乏可检测的补体介导的杀菌活性（滴度< 1：4）并且与增加的抗体亲合力相关的一些血清池观察到保护活性。因此，不仅C组抗体对脑膜炎球菌多糖疫苗的应答幅度随着年龄的增加而增加，而且对抗体功能活性也存在年龄相关的影响，使得免疫儿童比免疫成人需要更高的疫苗诱导抗体血清浓度来保护。
Serum bactericidal activity confers protection against meningococcal disease, but it is not known whether vaccine-induced anticapsular antibodies that lack bactericidal activity are protective. We developed an infant rat challenge model using a naturally occurring O-acetylated strain of Neisseria meningitidis group C and a strain that was negative for 0 acetylation (OAc). Rats 4 to 7 days of age inoculated intraperitoneally (i.p.) with similar to10(3) CFU of either strain developed >5 X 10(5) CFU/ml of blood obtained 18 h later. Dilutions of preimmunization sera given i.p. 2 h before the bacterial challenge had no effect on bacteremia, whereas group C anticapsular antibody in sera from adults immunized with meningococcal polysaccharide vaccine conferred complete or partial (>99% decrease in CFU per milliliter of blood) protection against the OAc-positive or OAc-negative strain, respectively, at antibody doses as low as 0.04 mug/rat. Anticapsular antibody at doses fivefold higher (0.18 to 0.2 mug/rat) in pooled sera from children immunized at a mean age of 2.6 years failed to protect rats, but antibody at the same or fivefold-lower dose in a serum pool from a group of children immunized at 4 years of age gave complete or partial protection. Protective activity was observed with some serum pools that lacked detectable complement-mediated bactericidal activity (titers < 1:4) and correlated with increasing antibody avidity. Thus, not only does the magnitude of the group C antibody response to meningococcal polysaccharide vaccine increase with increasing age but there are also age-related affects on antibody functional activity such that higher serum concentrations of vaccine-induced antibody are required for protection of immunized children than for immunized adults.