Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial.
Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial.
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DOI：
10.1016/s1473-3099(21)00128-6
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
EBL3001 study group
中科院分区：
文献类型：
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作者：
Afolabi MO;Ishola D;Manno D;Keshinro B;Bockstal V;Rogers B;Owusu-Kyei K;Serry-Bangura A;Swaray I;Lowe B;Kowuor D;Baiden F;Mooney T;Smout E;Köhn B;Otieno GT;Jusu M;Foster J;Samai M;Deen GF;Larson H;Lees S;Goldstein N;Gallagher KE;Gaddah A;Heerwegh D;Callendret B;Luhn K;Robinson C;Greenwood B;Leyssen M;Douoguih M;Leigh B;Watson-Jones D;EBL3001 study group
在埃博拉病毒病的病例和死亡中，儿童占很大比例。我们的目的是评估两剂异源疫苗方案的安全性和免疫原性，该方案包括编码埃博拉病毒糖蛋白的腺病毒26型载体疫苗（Ad26.ZEBOV）和编码埃博拉病毒、苏丹病毒和马尔堡病毒糖蛋白以及泰森林病毒核蛋白（mva - n - filo）的修饰痘苗安卡拉载体疫苗。这项随机、双盲、对照试验在塞拉利昂Kambia区的三个诊所进行。1-17岁的健康儿童和青少年被分为3个年龄组（12-17岁、4-11岁和1-3岁），并通过计算机生成的分组随机化（分组大小为8）随机分配（3:1），接受Ad26的肌肉注射。第57天（埃博拉疫苗组）接种ZEBOV （5 × 1010个病毒颗粒，第一剂），随后接种MVA-BN-Filo （1 × 108个感染单位，第二剂），或第57天接种脑膜炎球菌四价（a、C、W135和Y血清组）结合疫苗（MenACWY，第一剂），随后接种安慰剂（第二剂）（对照组）。研究小组人员（主要负责研究疫苗制备的人员除外）、参与者及其父母或监护人被蒙面研究疫苗分配。主要终点是安全性，衡量指标为每次接种疫苗后7天内主动出现的局部和全身不良症状、每次接种疫苗后28天内主动出现的全身不良事件、研究期间的异常实验室结果、以及整个研究期间的严重不良事件或立即报告的事件。次要结果是免疫原性（体液免疫反应），以第二次剂量后21天埃博拉病毒糖蛋白特异性结合抗体的浓度来测量。评估了所有接种过至少一剂研究疫苗并有可用的反应原性数据的参与者的主要结局，评估了所有在方案规定的时间窗口内接种过两种疫苗的参与者的免疫原性，至少有一个可评估的疫苗接种后样本，并且没有可能影响免疫反应的主要方案偏差。本研究注册在ClinicalTrials.gov, NCT02509494。从2017年4月4日至2018年7月5日，576名符合条件的儿童或青少年（三个年龄组各192名）被纳入并随机分配。在第一次和第二次给药后7天内，所有年龄组中最常见的局部不良事件是注射部位疼痛，频率范围从1-3岁注射安慰剂后儿童的0%（48例中没有一例）到Ad26后4-11岁儿童的21%（144例中的30例）。ZEBOV接种疫苗。在第一次和第二次给药后，在12-17岁和4-11岁年龄组中，7天内最常见的系统性不良事件是头痛，在第一次和第二次给药后，在1-3岁年龄组中出现发热。在所有年龄组中，不论疫苗类型如何，接种第一剂和第二剂疫苗后最常见的主动不良事件是疟疾。接种MenACWY后，在一名3岁的参与者中观察到严重的血小板减少症。在其他研究参与者中未观察到其他临床显著的实验室异常，也未报告与埃博拉疫苗方案相关的严重不良事件。没有与治疗相关的死亡。在134名12-17岁儿童中，131名（98%）（9929 ELISA单位[EU]/mL [95% CI 8172 - 12064]）、120名4-11岁儿童中119名（99%）（10 212 EU/mL[8419-12 388]）和121名1-3岁儿童中118名（98%）（22 568 EU/mL[18 426-27 642]）出现埃博拉病毒糖蛋白特异性结合抗体应答。Ad26。ZEBOV和MVA-BN-Filo埃博拉疫苗方案在1-17岁儿童中耐受性良好，无安全性问题，并诱导了强大的体液免疫反应，表明该方案适用于儿童埃博拉病毒病预防。创新药物倡议2联合企业和杨森疫苗和预防BV。
Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vectorbased vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children. Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.
尼日利亚儿童中10级肺炎球菌的安全性和免疫原性（PHID-CV）：促进剂量和2剂量追赶方案在生命的第二年中。
影响因子：
4.8
作者：
Odusanya OO;Kuyinu YA;Kehinde OA;Shafi F;François N;Yarzabal JP;Dobbelaere K;Rüggeberg JU;Borys D;Schuerman L
通讯作者：
Schuerman L