Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial
Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial
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DOI：
10.1016/s0140-6736(14)60842-4
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发表时间：
2014-12-13
期刊：
影响因子：
168.9
通讯作者：
Borrow, Ray
中科院分区：
文献类型：
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作者：
Read, Robert C.;Baxter, David;Borrow, Ray
背景脑膜炎球菌结合疫苗直接保护个体，但也可以通过阻断携带传播来提供群体保护。我们评估了脑膜炎球菌四价糖缀合物方法在这项3期、双盲、随机对照试验中，随机分配来自英格兰10个地点的18 - 24岁的大学生，（1 ∶ 1：1，区组大小为3），间隔1个月接种两剂日本脑炎疫苗（对照）、4CMenB或一个剂量的MenACWY-CRM，然后是安慰剂。参与者使用经验证的计算机生成的随机分配列表进行随机分配。参与者和结局评估者对治疗组不知情。从接种疫苗前采集的口咽拭子中分离出脑膜炎球菌，并在1年内按计划间隔5次。主要结果是每个疫苗疗程后1个月的横断面携带情况。次要结局包括主要分析后至研究终止的任何时间点的携带情况比较。在整个研究期间监测反应原性和不良事件。对改良的意向治疗人群进行了分析，该人群包括接受研究疫苗接种并在基线后提供至少一份可评估拭子的所有入组受试者。该试验在www.example.com注册，注册号为NCT 01214850。结果2010年9月21日至12月21日，2954名参与者被随机分配ClinicalTrials.gov 4CMenB组33%、MenACWY-CRM组34%和对照组31%在研究开始时脑膜炎球菌携带呈阳性。到1个月时，对照组和4CMenB（比值比1.2，95% CI 0.8 - 1.7）或MenACWY-CRM（0.9，[0.6 - 1.3]）组之间的携带率无显著差异。从第二次接种后3个月开始，4CMenB疫苗接种导致任何脑膜炎球菌菌株的携带率显著降低（18.2%[95% CI 3.4 - 30.8]携带减少），包囊组BCWY（26.6%[10.5 - 39.9]运载减少），包膜组CWY（29.6%[8.1 - 46.0]携带减少）和血清群CWY（28.5%[2.8 - 47.5]携带减少）。与对照组相比，MenACWY-CRM组的携带率也显著降低：血清群Y携带率降低39.0%（95%CI 17.3 - 55.0），血清群CWY携带率降低36.2%（15.6 - 51.7）。研究疫苗通常耐受良好，4CMenB组中一过性局部注射疼痛和肌痛的发生率增加。解释虽然我们在疫苗接种后1个月没有发现组间有显著差异，但MenACWY-CRM和4CMenB疫苗在接种后12个月内降低了脑膜炎球菌携带率，因此在广泛实施时可能会影响传播。
Background Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds.Methods In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to- treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850.Findings Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1.2, 95% CI 0.8-1.7) or MenACWY-CRM (0.9, [0.6-1.3]) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18.2% [95% CI 3.4-30.8] carriage reduction), capsular groups BCWY (26.6% [10.5-39.9] carriage reduction), capsular groups CWY (29.6% [8.1-46.0] carriage reduction), and serogroups CWY (28.5% [2.8-47.5] carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39.0% (95% CI 17.3-55.0) carriage reduction for serogroup Y and 36.2% (15.6-51.7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified.Interpretation Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented.