University of Tampere Medical School, Tampere, Finland.
N Engl J Med. 2011 Oct 13;365(15):1406-16. doi: 10.1056/NEJMoa1010331.
The efficacy of inactivated influenza vaccines is known to be poor in infants and young children.
We 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.
Attack 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.
Influenza 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.).
已证实流感灭活疫苗在婴儿和幼儿人群中的效果不佳。
我们研究了佐剂 MF59（一种油包水乳剂）对 4707 名 6 个月至不满 72 个月、既往未接种过流感疫苗的健康儿童接种三价流感灭活疫苗（TIV）的效果。儿童被随机分至三组，每组在两个连续的流感季节中，间隔 28 天接种两剂指定疫苗。两组分别给予相应年龄的 TIV 加或不加 MF59 佐剂，第三组给予对照（非流感）疫苗，以通过聚合酶链反应（PCR）检测来评估其针对流感样疾病的绝对和相对疗效。
两个流感季节的流感样疾病发生率分别为佐剂组 0.7%、非佐剂组 2.8%和对照组 4.7%。针对所有流感株（110 例中有 94 例是疫苗匹配的 H3N2 病毒）的绝对疫苗有效率，MF59 佐剂疫苗（ATIV）为 86%（95%置信区间 [CI]，74 至 93），无佐剂疫苗（TIV）为 43%（95% CI，15 至 61）；ATIV 相对于 TIV 的疫苗相对有效率为 75%（95% CI，55 至 87）。ATIV 在 6 个月至不满 36 个月儿童中的疗效为 79%（95% CI，55 至 90），在 36 至不满 72 个月儿童中的疗效为 92%（95% CI，77 至 97），而 TIV 分别为 40%（95% CI，-6 至 66）和 45%（95% CI，6 至 68）。ATIV 的抗体反应更高，并持续至第 181 天。在年龄较小的组中，有佐剂和无佐剂的流感疫苗的全身和局部反应发生率相似（相对风险，1.04；95% CI，0.98 至 1.09），但在年龄较大的组中，ATIV 接种后全身事件更常见（63%），而 TIV（44%）或对照疫苗（50%）接种后更常见。三组疫苗的严重不良事件分布均匀。
流感灭活疫苗加 MF59 佐剂对 PCR 确诊的婴儿和幼儿流感有效。（由诺华疫苗和诊断公司资助；临床试验编号，NCT00644059。）
