一种结合疫苗预防婴幼儿侵袭性b型流感嗜血杆菌疾病的随机、前瞻性现场试验。

A randomized, prospective field trial of a conjugate vaccine in the protection of infants and young children against invasive Haemophilus influenzae type b disease.

作者信息

Eskola J, Käyhty H, Takala A K, Peltola H, Rönnberg P R, Kela E, Pekkanen E, McVerry P H, Mäkelä P H

机构信息

National Public Health Institute, Helsinki, Finland.

出版信息

N Engl J Med. 1990 Nov 15;323(20):1381-7. doi: 10.1056/NEJM199011153232004.

DOI:10.1056/NEJM199011153232004

PMID:2233904

Abstract

BACKGROUND

Haemophilus influenzae type b is the leading cause of invasive bacterial disease in young children. The capsular polysaccharide vaccine does not protect children at greatest risk (those under the age of 18 months), but a polysaccharide-protein conjugate vaccine has proved to be more immunogenic in this age group.

METHODS

We enrolled 114,000 infants in Finland in an open, prospective, randomized trial of a H. influenzae type b capsular polysaccharide-diphtheria toxoid conjugate vaccine (polyribosylribitol phosphate-diphtheria toxoid [PRP-D]). Children born on odd-numbered days were vaccinated at the ages of 3, 4, 6, and 14 to 18 months; those born on even-numbered days formed the control group and received the same vaccine at the age of 24 months.

RESULTS

After three doses of the vaccine there were 4 cases of verified bacteremic H. influenzae type b disease in the group receiving early vaccination, as compared with 64 cases in the control group, between the ages of approximately 7 and 24 months. The protective efficacy of the vaccine was thus 94 percent (95 percent confidence interval, 83 to 98). No serious adverse effects were reported. The immune response to the conjugate vaccine was characteristic of a T-cell-dependent response when studied in a cohort of 120 infants. The primary immunization series resulted in a geometric mean concentration of anticapsular antibody of 0.53 micrograms per milliliter at the age of seven months, and the fourth dose evoked an anamnestic response, with a mean antibody concentration of 45.22 micrograms per milliliter.

CONCLUSIONS

A new conjugate vaccine consisting of the capsular polysaccharide of H. influenzae type b covalently linked to a protein carrier (PRP-D), administered to infants beginning at the age of 3 months, is highly effective in protecting young Finnish children (7 to 24 months old) against invasive H. influenzae type b infections.

摘要

背景

b型流感嗜血杆菌是幼儿侵袭性细菌疾病的主要病因。荚膜多糖疫苗不能保护风险最高的儿童（18个月以下的儿童），但一种多糖-蛋白质结合疫苗已被证明在这个年龄组中具有更强的免疫原性。

方法

我们在芬兰招募了114,000名婴儿，进行一项关于b型流感嗜血杆菌荚膜多糖-白喉类毒素结合疫苗（多聚核糖磷酸-白喉类毒素[PRP-D]）的开放性、前瞻性、随机试验。奇数日出生的儿童在3、4、6和14至18个月龄时接种疫苗；偶数日出生的儿童组成对照组，在24个月龄时接种相同疫苗。

结果

在大约7至24个月龄期间，早期接种疫苗组在接种三剂疫苗后有4例确诊的b型流感嗜血杆菌菌血症疾病病例，而对照组有64例。因此，疫苗的保护效力为94%（95%置信区间，83%至98%）。未报告严重不良反应。在一组120名婴儿中进行研究时，对结合疫苗的免疫反应具有T细胞依赖性反应的特征。初次免疫系列在7个月龄时产生的抗荚膜抗体几何平均浓度为每毫升0.53微克，第四剂引发了回忆反应，平均抗体浓度为每毫升45.22微克。