Immunogenicity and Tolerability of Recombinant Serogroup B Meningococcal Vaccine Administered With or Without Routine Infant Vaccinations According to Different Immunization Schedules A Randomized Controlled Trial
Immunogenicity and Tolerability of Recombinant Serogroup B Meningococcal Vaccine Administered With or Without Routine Infant Vaccinations According to Different Immunization Schedules A Randomized Controlled Trial
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DOI：
10.1001/jama.2012.85
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发表时间：
2012-02-08
影响因子：
120.7
通讯作者：
Pollard, Andrew J.
中科院分区：
文献类型：
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作者：
Gossger, Nicoletta;Snape, Matthew D.;Pollard, Andrew J.
背景在缺乏有效疫苗的情况下，血清群B脑膜炎奈瑟菌（MenB）仍然是发达国家儿童早期侵袭性疾病的主要原因。目的确定多组分MenB疫苗（4 CMen B）和常规婴儿疫苗同时或单独接种时的免疫原性和反应原性。设计、设置和参与者2B期、多中心、开放标签、平行组、2008年8月至2010年7月，在欧洲对1885名2个月大的婴儿进行了随机对照研究。干预参与者按2：2：1的比例随机分组：1例在2、4和6个月时接受（1）4CMenB和常规疫苗（7价肺炎球菌和混合白喉、破伤风、无细胞百日咳、灭活脊髓灰质炎、B型肝炎、B型流感嗜血杆菌疫苗）;（2）在2、4和6个月时接种4CMenB，并在3、5和7个月时接种常规疫苗;或（4）在2，3，主要结果测量人补体血清杀菌活性（hSBA）滴度为1：结果在3次4CMenB疫苗接种后，99%或更多的婴儿产生针对菌株44/76-SL和5/99的1：5或更高的hSBA滴度。对于NZ 98/254，这一比例为79%（95% CI，75.2%-82.4%），常规疫苗接种2、4和6个月时，86.1%（95% CI，82.9%-89.0%），常规疫苗接种2、3和4个月时为81.7%（95% CI，76.6%-86.2%）。除了对培洛芬和血清型6 B肺炎球菌多糖的反应外，对常规疫苗给予4CMenB的反应不劣于单独使用常规疫苗的所有抗原。当单独给药时，在26%（158/602）至41%（247/607）的4CMenB剂量后观察到发热，而单独接种常规疫苗后为23%（69/304）至36%（109/306），单独接种常规疫苗后为51%（306/605）至61%（380/624）结论4CMenB疫苗在2、4、6月龄或2、3、4月龄与常规疫苗联合接种时，对参考株具有免疫原性，对常规婴儿疫苗接种的反应产生最小的干扰。
Context In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries.Objective To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately.Design, Setting, and Participants Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe.Intervention Participants were randomized 2: 2: 1: 1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months.Main Outcome Measures Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1: 5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99).Results After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1: 5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together.Conclusion A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations.