Oil-in-Water Emulsion Adjuvant with Influenza Vaccine in Young Children
Oil-in-Water Emulsion Adjuvant with Influenza Vaccine in Young Children
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DOI：
10.1056/nejmoa1010331
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发表时间：
2011-10-13
影响因子：
158.5
通讯作者：
Clemens, Ralf
中科院分区：
文献类型：
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作者：
Vesikari, Timo;Knuf, Markus;Clemens, Ralf
背景灭活流感疫苗在婴幼儿中的效果较差。方法我们研究了水包油乳剂MF59对4707名6至72个月以下未接种过流感疫苗的健康儿童的三价灭活流感疫苗(TIV)效果的影响。这些儿童被随机分配到三个研究组，在连续的两个流感季节，每个研究组分别接种两剂疫苗，相隔28天。其中两组接种了适龄剂量的TIV，加或不加MF59佐剂，第三组接种对照(非流感)疫苗，以评估其对流感样疾病的绝对和相对有效性，经聚合酶链式反应(PCR)分析证实。结果在两个流感季节，佐剂疫苗组、非佐剂疫苗组和对照疫苗组流感样疾病的发病率分别为0.7%、2.8%和4.7%。MF59佐剂疫苗(ATIV)和无佐剂疫苗(TIV)对所有流感病毒株的绝对有效率分别为86%(95%可信区间，74~93)和43%(95%CI，15~61)，ATIV与TIV的相对有效率为75%(95%CI，55~87)。ATIV在6~36个月和36~72个月以下儿童的有效率分别为79%(95%CI，55~90)和92%(95%CI，77~97)，而TIV的有效率分别为40%(95%CI，-6~66)和45%(95%CI，6~68)。ATIV的抗体反应较高，并持续到第181天。年轻年龄组接种与不接种佐剂的流感疫苗的全身和局部反应发生率相似(相对危险度为1.04；95%可信区间为0.98~1.09)，但老年组接种ATIV后的全身反应发生率(63%)高于接种TIV或对照疫苗后的全身反应发生率(44%)或对照组(50%)。严重不良事件平均分布在三个疫苗组中。结论含有MF59佐剂的流感疫苗对聚合酶链式反应确诊的婴幼儿流感有效。(由诺华疫苗和诊断公司提供资金；ClinicalTrials.gov编号，NCT00644059。)
BACKGROUNDThe efficacy of inactivated influenza vaccines is known to be poor in infants and young children.METHODSWe studied the effect of the adjuvant MF59, an oil-in-water emulsion, on the efficacy of trivalent inactivated influenza vaccine (TIV) in 4707 healthy children 6 to less than 72 months of age who had not previously been vaccinated against influenza. The children were randomly assigned to three study groups, each of which received the assigned vaccines in two doses, 28 days apart, during two consecutive influenza seasons. Two of the groups were given age-appropriate doses of TIV either with or without the MF59 adjuvant, and the third group was given control (noninfluenza) vaccines to assess their absolute and relative efficacy against influenza-like illness, as confirmed by means of polymerase-chain-reaction (PCR) assay.RESULTSAttack rates of influenza-like illness across both influenza seasons were 0.7%, 2.8%, and 4.7% in the adjuvant, nonadjuvant, and control vaccine groups, respectively. The absolute vaccine efficacy rates against all influenza strains (94 of 110 cases were due to vaccine-matched H3N2 viruses) were 86% (95% confidence interval [CI], 74 to 93) for the MF59-adjuvant vaccine (ATIV) and 43% (95% CI, 15 to 61) for the vaccine without the adjuvant (TIV); the relative vaccine efficacy rate for ATIV versus TIV was 75% (95% CI, 55 to 87). The efficacy rates for ATIV were 79% (95% CI, 55 to 90) in children 6 to less than 36 months of age and 92% (95% CI, 77 to 97) in those 36 to less than 72 months of age, as compared with 40% (95% CI, -6 to 66) and 45% (95% CI, 6 to 68), respectively, for TIV. Antibody responses were higher with ATIV and remained so through day 181. The rates of systemic and local reactions to the influenza vaccines with and without the adjuvant were similar in the younger age group (relative risk, 1.04; 95% CI, 0.98 to 1.09), but systemic events in the older age group were more frequent after administration of ATIV (63%) than after administration of TIV (44%) or the control vaccine (50%). Serious adverse events were distributed evenly across the three vaccine groups.CONCLUSIONSInfluenza vaccine with the MF59 adjuvant is efficacious against PCR-confirmed influenza in infants and young children. (Funded by Novartis Vaccines and Diagnostics; ClinicalTrials.gov number, NCT00644059.)