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一种研究性四价脑膜炎奈瑟菌-白喉类毒素结合疫苗在两岁儿童中引发的C群抗荚膜抗体的保护活性。

Protective activity of group C anticapsular antibodies elicited in two-year-olds by an investigational quadrivalent Neisseria meningitidis-diphtheria toxoid conjugate vaccine.

作者信息

Granoff Dan M, Harris Shannon L

机构信息

Children's Hospital Oakland Research Institute, Oakland, CA, USA.

出版信息

Pediatr Infect Dis J. 2004 Jun;23(6):490-7. doi: 10.1097/01.inf.0000129686.12470.e6.

Abstract

BACKGROUND

Quadrivalent capsular group A, C, Y and W-135 meningococcal conjugate (MC-4) vaccines are under development

OBJECTIVE

Predict efficacy of an investigational MC-4 vaccine in 2-year-old children for prevention of group C disease.

DESIGN

Measurement of group C antibody concentrations, avidity and bactericidal and passive protective activity in sera from 2-year-olds given 1 dose of MC-4 vaccine (N = 30) and 3-year-olds (N = 30) and adults (N = 26) given 1 dose of meningococcal polysaccharide (MPS-4) vaccine.

RESULTS

One month after vaccination, the geometric mean anticapsular antibody concentration of children given MC-4 vaccine (3.1 microg/ml) was lower than that of control children (5.1 microg/ml; P < 0.04) or adults immunized with MPS-4 vaccine (22.9 microg/ml; P < 0.001). However, the percent of sera with protective bactericidal titers of >/=1/4 was higher in children given MC-4 vaccine (50%, versus 17% in children given MPS-4 vaccine; P < 0.02) and was not significantly different from that of immunized adults (65%). In children, the mean antibody avidity at 1 month was higher in the MC-4 group (22 nM versus 16 nM in the MPS-4 group; P = 0.002), and at 6 months increased in the MC-4 group (28 nM; P < 0.001), but not in the MPS-4 vaccine group (17 nM). Higher avidity antibody gave greater passive protection in the infant rat bacteremia model than did lower avidity antibody (P < 0.03).

CONCLUSIONS

Although MPS-4 vaccine elicited higher group C serum antibody concentrations in 3-year-olds than did MC-4 vaccine in 2-year-olds, the higher antibody avidity after MC-4 vaccine resulted in higher bactericidal and passive protective activity.

摘要

背景

四价A、C、Y和W-135群脑膜炎球菌结合疫苗(MC-4)正在研发中。

目的

预测一种研究性MC-4疫苗在2岁儿童中预防C群疾病的效果。

设计

测量给予1剂MC-4疫苗的2岁儿童(N = 30)、给予1剂脑膜炎球菌多糖(MPS-4)疫苗的3岁儿童(N = 30)和成人(N = 26)血清中C群抗体浓度、亲和力以及杀菌和被动保护活性。

结果

接种疫苗1个月后,给予MC-4疫苗的儿童的几何平均抗荚膜抗体浓度(3.1微克/毫升)低于对照儿童(5.1微克/毫升;P < 0.04)或接种MPS-4疫苗的成人(22.9微克/毫升;P < 0.001)。然而,杀菌效价≥1/4的血清百分比在给予MC-4疫苗的儿童中更高(50%,而给予MPS-4疫苗的儿童为17%;P < 0.02),且与免疫成人(65%)无显著差异。在儿童中,MC-4组1个月时的平均抗体亲和力更高(22纳摩尔,而MPS-4组为16纳摩尔;P = 0.002),且在MC-4组中6个月时升高(28纳摩尔;P < 0.001),但MPS-4疫苗组未升高(17纳摩尔)。在幼鼠菌血症模型中,高亲和力抗体比低亲和力抗体提供了更强的被动保护(P < 0.03)。

结论

尽管MPS-4疫苗在3岁儿童中诱导的C群血清抗体浓度高于MC-4疫苗在2岁儿童中诱导的浓度,但MC-4疫苗接种后更高的抗体亲和力导致了更高的杀菌和被动保护活性。

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