Eskola J, Olander R M, Hovi T, Litmanen L, Peltola S, Käyhty H
National Public Health Institute, Helsinki, Finland.
Lancet. 1996;348(9043):1688-92. doi: 10.1016/S0140-6736(96)04356-5.
Inclusion of new vaccines in vaccination programmes for children would be easier if they could be combined with existing vaccines. Vaccines containing acellular pertussis in the diphtheria/tetanus/pertussis (DTP-a) combination are expected to replace the conventional whole-cell vaccines (DTP-w). We tested the immunogenicity and safety of a combination of DTP-a with the Haemophilus influenzae type b (Hib) conjugate of Hib capsular polysaccharide and tetanus toxid (PRP-T), and inactivated poliovirus vaccine (i.p.v.).
120 infants were enrolled and randomised to four groups to receive DTP-a at ages 2, 4, and 6 months. At 4 and 6 months they also received Hib conjugate and i.p.v., either as separate injections or mixed with DTP-a. All injections were given intramuscularly in the anterolateral area of the thigh. Any reactions after each vaccination were noted by the parents. EIA was used to measure titres of diphtheria, tetanus, and pertussis antibodies, RIA for Hib anticapsular antibodies, and microneutralisation assay for poliovirus antibodies from serum samples collected at the ages of 2, 4, 6, and 7 months.
There were 30 infants in each group. Only mild adverse events were reported. There was a tendency towards slightly lower concentrations of filamentous haemagglutinin, tetanus, and poliovirus 1 antibodies when the vaccines were mixed. However, there was a more pronounced difference (p = 4 x 10(-6)) in Hib antibodies between groups receiving Hib capsular polysaccharide mixed with DTP-a (geometric mean concentrations 0.37 microgram/mL and 0.56 microgram/mL) compared with groups receiving the vaccines separately (3.10 micrograms/mL and 3.94 micrograms/mL).
Administration of premixed DTP-a, Hib conjugate, and i.p.v. affect the immune response significantly. The mechanism of this interference is not clear. The immunogenicity of all antigens must be tested before new combinations can be accepted for vaccination programmes for infants.
如果新疫苗能够与现有疫苗联合使用，那么将其纳入儿童疫苗接种计划会更加容易。含有无细胞百日咳的白喉/破伤风/百日咳（DTP-a）联合疫苗有望取代传统的全细胞疫苗（DTP-w）。我们测试了DTP-a与b型流感嗜血杆菌（Hib）结合的Hib荚膜多糖和破伤风类毒素（PRP-T）以及灭活脊髓灰质炎病毒疫苗（i.p.v.）联合使用的免疫原性和安全性。
招募120名婴儿并随机分为四组，在2、4和6月龄时接种DTP-a。在4和6月龄时，他们还接受Hib结合疫苗和i.p.v.，要么单独注射，要么与DTP-a混合注射。所有注射均在大腿前外侧区域进行肌肉注射。每次接种后父母记录任何反应。采用酶免疫分析法（EIA）检测2、4、6和7月龄时采集的血清样本中白喉、破伤风和百日咳抗体的滴度，采用放射免疫分析法（RIA）检测Hib抗荚膜抗体，采用微量中和试验检测脊髓灰质炎病毒抗体。
每组有30名婴儿。仅报告了轻度不良事件。疫苗混合使用时，丝状血凝素、破伤风和脊髓灰质炎病毒1抗体的浓度有略低的趋势。然而，与分别接种疫苗的组（几何平均浓度为3.10微克/毫升和3.94微克/毫升）相比，接受与DTP-a混合的Hib荚膜多糖的组之间Hib抗体有更显著的差异（p = 4×10⁻⁶）（几何平均浓度为0.37微克/毫升和0.56微克/毫升）。
预混合的DTP-a、Hib结合疫苗和i.p.v.的接种会显著影响免疫反应。这种干扰的机制尚不清楚。在新的联合疫苗被接受用于婴儿疫苗接种计划之前，必须对所有抗原的免疫原性进行测试。
