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首页> 外文期刊>The Lancet >Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: Results of two randomised trials
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Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: Results of two randomised trials

机译：伴随常规婴儿和儿童疫苗接种的免疫原性和安全性，重组，脑膜炎球菌血清群B疫苗（4cmeNb）：两项随机试验的结果

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Background Meningococcal serogroup B disease disproportionately affects infants. We assessed lot-to-lot consistency, safety and immunogenicity, and the effect of concomitant vaccination on responses to routine vaccines of an investigational multicomponent vaccine (4CMenB) in this population. Methods We did primary and booster phase 3 studies between March 31, 2008, and Aug 16, 2010, in 70 sites in Europe. We used two series of sponsor-supplied, computer-generated randomisation envelopes to allocate healthy 2 month-old infants to receive routine vaccinations (diphtheria-tetanus-acellular pertussis, inactivated poliovirus, hepatitis B plus Haemophilus influenzae type b, and seven-valent pneumococcal vaccine) wat 2, 4, and 6 months of age alone, or concomitantly with 4CMenB or serogroup C conjugate vaccine (MenC) in: 1) an open-label, lot-to-lot immunogenicity and safety substudy of three 4CMenB lots compared with routine vaccines alone (1:1:1:1, block size eight); or 2) an observer-blind, lot-to-lot safety substudy of three 4CMenB lots compared with MenC (1:1:1:3, block size six). At 12 months, 4CMenB-primed children from either substudy were randomised (1:1, block size two) to receive 4CMenB booster, with or without measles-mumps-rubella-varicella (MMRV) vaccine. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroup B test strains, and on randomly selected subsets of serum samples for routine vaccines; laboratory personnel were masked to assignment. The first coprimary outcome was lot-to-lot consistency (hSBA geometric mean ratio of all lots between 0.5 and 2.0), and the second was an immune response (hSBA titre.5) for each of the three strains. The primary outcome for the booster study was immune response to booster dose. Immunogenicity data for 4CMenB were for the modified intention-totreat population, including all infants from the open-label substudy who provided serum samples. The safety population included all participants who contributed safety data after at least one dose of study vaccine. These trials are registered with ClinicalTrials.gov, numbers NCT00657709 and NCT00847145. Findings We enrolled 2627 infants in the open-label phase, 1003 in the observer-blind phase, and 1555 in the booster study. Lot-to-lot consistency was shown for the three 4CMenB lots, with the lowest 95% lower confidence limit being 0-E74 and the highest upper limit being 1.33. Of 1181.1184 infants tested 1 month after three 4CMenB doses (all lots pooled), 100% (95% CI 99.100) had hSBA titres of 5 or more against strains selective for factor H binding protein and neisserial adhesin A, and 84% (82.86) for New Zealand outer-membrane vesicle. In a subset (n=100), 84% (75.91) of infants had hSBA titres of 5 or more against neisseria heparin binding antigen. At 12 months of age, waning titres were boosted by a fourth dose, such that 95.100% of children had hSBA titres of 5 or more for all antigens, with or without concomitant MMRV. Immune responses to routine vaccines were much the same with or without concomitant 4CMenB, but concomitant vaccination was associated with increased reactogenicity. 77% (1912 of 2478) of infants had fever of 38.5-C or higher after any 4CMenB dose, compared with 45% (295 of 659) after routine vaccines alone and 47% (228 of 490) with MenC, but only two febrile seizures were deemed probably related to 4CMenB. Interpretation 4CMenB is immunogenic in infants and children aged 12 months with no clinically relevant interference with routine vaccines, but increases reactogenicity when administered concomitantly with routine vaccines. This breakthrough vaccine offers an innovative solution to the major remaining cause of bacterial meningitis in infant and toddlers. Funding Novartis Vaccines and Diagnostics.
机译：背景脑膜炎球菌血清群B疾病不成比例地影响婴儿。我们评估了批次到批次的一致性，安全性和免疫原性，以及伴随疫苗接种对该群体中的研究多组分疫苗（4cmeNB）的常规疫苗的反应。方法我们在2008年3月31日和2010年3月16日期间在欧洲70个地点进行了初级和助推期第3项研究。我们使用了两次赞助商提供的计算机生成的随机信封，分配健康的2个月大婴幼儿，接受常规疫苗接种（白喉 - 破伤风 - 无细胞植物，灭活的脊髓灰质炎，乙型肝炎加上嗜血杆菌型B型，和七价肺炎单独疫苗）Wat 2,4和6个月的年龄，或伴随着4cmenb或血清组c共轭疫苗（menc）：1）与3个4cmenb批次的开放标签，批次批量免疫原性和安全归档相比单独常规疫苗（1：1：1：1，块尺寸8）;或2）与MENC相比，观察者 - 盲，三个4CMENB批量的批量安全拼盘（1：1：1：3，块大小六）。在12个月内，从替换物中的4cmenB引发的儿童随机化（1：1，块尺寸两尺寸），以接收4cmenb助推器，有或没有麻疹-mumps-surbella-variCella（mmrv）疫苗。通过对血群B试管的血清杀菌试验（HSBA）进行血清杀菌测定评估免疫原性，以及用于常规疫苗的随机选择的血清样品的亚群;实验室人员被屏蔽了分配。第一个组合结果是批量批次（HSBA几何平均比例在0.5和2.0之间的所有批次），第二种是三种菌株中的每一个的免疫应答（HSBA TITRE.5）。增强性研究的主要结果是对增强剂量的免疫反应。 4CmEnb的免疫原性数据用于改性意图 - Totreat群体，包括来自提供血清样品的开放标签血底的所有婴儿。安全人群包括所有参与者在至少一剂研究疫苗后贡献安全数据。这些试验在ClinicalTrials.gov中注册，NCT00657709和NCT00847145。调查结果我们在开放标签阶段参加了2627名婴儿，在观察者盲阶段1003中，加强研究中的1555年。对于三个4CMENB批量显示了批次到批次的一致性，最低的95％较低的置信度限制为0-E74，最高上限为1.33。 1181.11841184婴儿在三个4cmenb剂量后1个月测试（汇集的所有批量），100％（95％CI 99.100）的HSBA滴度有5个或更多的针对因子H结合蛋白和Neisserial粘附蛋白A的菌株和84％（82.86）对于新西兰外膜囊泡。在子集（n = 100）中，84％（75.91）次婴儿的婴儿5或以上的HSBA滴度对抗Neisseria肝素结合抗原。在12个月的年龄时，通过第四剂量促进了滴度，使95.100％的儿童为所有抗原的HSBA滴度为5或更多，有或没有伴随的MMRV。对常规疫苗的免疫应答与4cmeNB的常规疫苗相同，但伴随的疫苗接种与转速增加有关。在任何4cmenb剂量后，77％（1912年）的婴儿发烧38.5-c或更高，与单独的常规疫苗和47％（228个中490个）的45％（295％），但只有两种发热癫痫发作可能与4cmenb相关。解释4CMENB在12个月内的婴儿和儿童免疫原性，没有临床相关干扰常规疫苗，但在常规疫苗施用时增加反应性。这种突破性疫苗为婴儿和幼儿的细菌性脑膜炎的主要原因提供了一种创新的解决方案。资助诺华疫苗和诊断。

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  • 来源
    《The Lancet》 |2013年第9869期|共11页
  • 作者

    VesikariT.; EspositoS.; PrymulaR.; YpmaE.; KohlI.; ToneattoD.; DullP.; KimuraA.;

  • 作者单位

    University of Tampere Medical School Vaccine Research Centre 33014 Tampere Finland;

    Pediatric Clinic 1 University of Milan Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico;

    University Hospital Hradec Kralove Hradec Kralove Czech Republic;

    Novartis Vaccines and Diagnostics Cambridge MA United States;

    Novartis Vaccines and Diagnostics Cambridge MA United States;

    Novartis Vaccines and Diagnostics Cambridge MA United States;

    Novartis Vaccines and Diagnostics Cambridge MA United States;

    Novartis Vaccines and Diagnostics Cambridge MA United States;

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  • 正文语种 eng
  • 中图分类 医药、卫生;
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