Safety and immunogenicity of an inactivated influenza A/H5N1 vaccine given with or without aluminum hydroxide to healthy adults: Results of a phase I-II randomized clinical trial
Safety and immunogenicity of an inactivated influenza A/H5N1 vaccine given with or without aluminum hydroxide to healthy adults: Results of a phase I-II randomized clinical trial
复制标题
DOI：
10.1086/592172
复制
发表时间：
2008-11-01
影响因子：
6.4
通讯作者：
Hill, Heather
中科院分区：
文献类型：
--
作者：
Keitel, Wendy A.;Campbell, James D.;Hill, Heather
背景。正在探索预防大流行性流感疫苗的剂量节约战略。我们评价了氢氧化铝（AlOH）佐剂的剂量节约潜力。总共600名健康受试者（年龄在18-49岁）被随机分为两组，每组间隔1个月接种含7.5、15或45 μ g血凝素（HA）的亚病毒粒子灭活甲型流感/H5N1疫苗，含或不含600 μ g氢氧化铝（AlOH），或3.75 μ g HA，含或不含300 μ g AlOH。每次接种前和接种后1个月分别取血清标本进行抗体检测。所有配方都是安全的。注射部位不适在接种AlOH疫苗组更常见。两种疫苗接种后，抗体反应均呈剂量相关增加（P < 0.001）：含AlOH和不含AlOH疫苗的血凝抑制抗体几何平均滴度分别为：接种3.75 μ g HA的受试者为5.4和5.4，接种7.5 μ g HA的受试者为7.7和5.3，接种15 μ g HA的受试者为8.1和8.5，接种45 μ g HA的受试者为14.8和12。在有或没有AlOH的情况下接受3.75 μ g HA的受试者中，分别有2%和2%的受试者滴度增加>= 4倍；接受7毫克HA治疗的分别为14%和0%；分别有14%和13%的人接受了15毫克的HA；33%和25%的人接受45毫克HA。添加AlOH仅能增强接受7.5 μ g HA的受试者的反应，而不添加AlOH的接受7.5 μ g HA的受试者的反应出乎意料地低。总的来说，没有观察到AlOH佐剂有意义的有益作用。试验注册。ClinicalTrials.govidentifier: NCT00296634。
Background. Dose-sparing strategies are being explored for vaccines against pandemic influenza. We evaluated the dose-sparing potential of aluminum hydroxide (AlOH) adjuvant.Methods. A total of 600 healthy subjects (age, 18-49 years) were randomized to receive 2 vaccinations 1 month apart with subvirion inactivated influenza A/H5N1 vaccine containing 7.5, 15, or 45 mu g of hemagglutinin (HA), with or without 600 mu g of aluminum hydroxide (AlOH), or 3.75 mu g of HA, with or without 300 mu g of AlOH. Serum specimens were obtained for antibody assays before and 1 month after each vaccination.Results. All formulations were safe. Injection site discomfort was more frequent in groups given vaccines with AlOH. Dose-related increases in antibody responses were noted after both vaccinations (P < .001): geometric mean titers of hemagglutination inhibition antibody in vaccines with and without AlOH, respectively, were 5.4 and 5.4 for subjects who received 3.75 mu g of HA, 7.7 and 5.3 for those who received 7.5 mu g of HA, 8.1 and 8.5 for those who received 15 mu g of HA, and 14.8 and 12 for those who received 45 mu g of HA. A >= 4-fold increase in titer was observed in 2% and 2% of subjects who received 3.75 mu g of HA with or without AlOH, respectively; in 14% and 0% who received 7 mu g of HA; in 14% and 13% who received 15 mu g of HA; and in 33% and 25% who received 45 mu g of HA. Addition of AlOH enhanced responses only for subjects who received 7.5 mu g of HA, but responses in subjects who received 7.5 mu g of HA without AlOH were unexpectedly low.Conclusion. Overall, a meaningful beneficial effect of AlOH adjuvant was not observed.Trial registration. ClinicalTrials.govidentifier: NCT00296634.