Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia
Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia
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DOI：
10.1016/s2214-109x(16)30075-4
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发表时间：
2016-08-01
影响因子：
34.3
通讯作者：
Kampmann, Beate
中科院分区：
文献类型：
--
作者：
Clarke, Ed;Saidu, Yauba;Kampmann, Beate
背景脊髓灰质炎病毒灭活疫苗（IPV）的引入是根除脊髓灰质炎的关键一步。本试验研究了IPV的安全性和免疫原性，同时给予麻疹，风疹和黄热病疫苗在9个月时，作为一个完整的或部分剂量使用针头和注射器或一次性注射器喷射injector.Methods我们做了第4期，随机，非劣效性试验在冈比亚西部的三个城郊政府诊所。已经接受口服脊髓灰质炎病毒疫苗的9-10个月婴儿被随机分配接受IPV、麻疹-风疹和黄热病疫苗，单独或联合接种。单独地，在第二次访视时通过针头和注射器或一次性注射器喷射注射器给予IPV作为完全肌内或部分皮内剂量。主要结果为接种疫苗后4-6周脊髓灰质炎病毒的血清阳性率和基线与接种疫苗后麻疹、风疹和黄热病血清样本之间的血清转换率;以及针对疫苗每种成分产生的接种后抗体滴度。我们进行了符合方案分析，脊髓灰质炎病毒血清阳性率和麻疹、风疹和黄热病血清转换的非劣效性界值为10%，log（2）转换抗体滴度的非劣效性界值为1/3 log（2）。该试验注册于ClinicalTrials.gov，编号NCT 01847872。结果在2013年7月10日至2014年5月8日期间，我们评估了1662名婴儿的合格性，其中1504名被纳入7个疫苗干扰组之一和4个分次给药和替代给药途径组之一。联合给药降低了风疹和黄热病抗体滴度，但两种情况下的血清转换率均达到非劣效性（风疹，-4.5% [95% CI-9.5至-0.1];黄热病，1.2% [-2.9至5.5]）。麻疹和脊髓灰质炎病毒应答未受影响（麻疹，6.8% [95% CI -1.4至14.9];脊髓灰质炎病毒血清1型，1.6% [-6.7至4.7];血清2型，0.0% [-2.1至2.1];血清3型，0.0% [-3.8至3.9]）。疫苗接种后脊髓灰质炎病毒血清阳性率普遍较高（> 97%），但与全剂量相比，部分皮内剂量IPV产生的抗体滴度并未达到非劣效性。通过皮内途径，血清转化或滴度升高4倍的婴儿数量也较低。数据支持在9个月的扩大免疫规划时间表内，IPV，麻疹-风疹和黄热病疫苗的未来共同管理。通过针头和注射器或一次性注射器喷射注射器进行IPV单次皮内分次给药会损害所产生的免疫力，尽管其导致接种后脊髓灰质炎病毒血清阳性率较高。版权所有（C）克拉克等人。开放获取文章根据CC BY的条款分发。
Background 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.Methods 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) log(2) for log(2)-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872.Findings 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.Interpretation 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. Copyright (C) Clarke et al. Open Access article distributed under the terms of CC BY.