MRC Unit The Gambia, Fajara, Banjul, The Gambia.
MRC Unit The Gambia, Fajara, Banjul, The Gambia.
Lancet Glob Health. 2016 Aug;4(8):e534-47. doi: 10.1016/S2214-109X(16)30075-4. Epub 2016 Jun 27.
The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector.
We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9-10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles-rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4-6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872.
Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, -4·5% [95% CI -9·5 to -0·1]; yellow fever, 1·2% [-2·9 to 5·5]). Measles and poliovirus responses were unaffected (measles, 6·8% [95% CI -1·4 to 14·9]; poliovirus serotype 1, 1·6% [-6·7 to 4·7]; serotype 2, 0·0% [-2·1 to 2·1]; serotype 3, 0·0% [-3·8 to 3·9]). Poliovirus seroprevalence was universally high (>97%) after vaccination, but the antibody titres generated by fractional intradermal doses of IPV did not achieve non-inferiority compared with full dose. The number of infants who seroconverted or had a four-fold rise in titres was also lower by the intradermal route. There were no safety concerns.
The data support the future co-administration of IPV, measles-rubella, and yellow fever vaccines within the Expanded Programme on Immunization schedule at 9 months. The administration of single fractional intradermal doses of IPV by needle and syringe or disposable-syringe jet injector compromises the immunity generated, although it results in a high post-vaccination poliovirus seroprevalence.
Bill & Melinda Gates Foundation.
灭活脊灰病毒疫苗（IPV）的引入是脊灰根除终局的关键步骤。本试验在冈比亚西部的三个城市郊区政府诊所进行了一项 4 期、随机、非劣效性试验。已经接受过口服脊灰病毒疫苗的 9-10 月龄婴儿随机接受 IPV、麻疹-风疹和黄热病疫苗单独或联合接种。此外，在第二次就诊时，通过针和注射器或一次性注射器喷射注射器以全剂量或半剂量肌内或皮内给予 IPV。主要结局是接种后 4-6 周脊灰病毒血清阳性率以及麻疹、风疹和黄热病基线和接种后血清样本之间的血清转化率；以及针对疫苗各成分产生的接种后抗体滴度。我们进行了一项方案分析，脊灰病毒血清阳性率和麻疹、风疹和黄热病血清转化率的非劣效性边缘为 10%，对数 2 转换的抗体滴度的非劣效性边缘为（1/3）log2。本试验在 ClinicalTrials.gov 注册，编号为 NCT01847872。
2013 年 7 月 10 日至 2014 年 5 月 8 日，我们评估了 1662 名婴儿的入选资格，其中 1504 名婴儿被纳入 7 组疫苗干扰组和 4 组分剂量和替代给药途径组之一。风疹和黄热病抗体滴度因联合使用而降低，但在这两种情况下，血清转化率均达到非劣效性（风疹，-4.5%[95%CI -9.5 至 -0.1]；黄热病，1.2%[-2.9 至 5.5]）。麻疹和脊灰病毒的反应不受影响（麻疹，6.8%[95%CI -1.4 至 14.9]；脊灰病毒血清型 1，1.6%[-6.7 至 4.7]；血清型 2，0.0%[-2.1 至 2.1]；血清型 3，0.0%[-3.8 至 3.9]）。脊灰病毒血清阳性率普遍较高（>97%），但与全剂量相比，IPV 分剂量皮内接种产生的抗体滴度未达到非劣效性。皮内途径的血清转化率和 4 倍升高的婴儿数量也较低。没有安全性问题。
数据支持在扩大免疫规划计划中，9 个月龄时同时接种 IPV、麻疹-风疹和黄热病疫苗。虽然通过针和注射器或一次性注射器喷射注射器进行单次皮内分剂量 IPV 接种可导致免疫效果降低，但脊灰病毒接种后的血清阳性率仍然很高。
比尔及梅琳达·盖茨基金会。
