High-dose trivalent influenza vaccine compared to standard dose vaccine in elderly adults: Safety, immunogenicity and relative efficacy during the 2009-2010 season
High-dose trivalent influenza vaccine compared to standard dose vaccine in elderly adults: Safety, immunogenicity and relative efficacy during the 2009-2010 season
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DOI：
10.1016/j.vaccine.2012.12.013
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发表时间：
2013-01-30
期刊：
影响因子：
5.5
通讯作者：
Talbot, H. Keipp
中科院分区：
文献类型：
--
作者：
DiazGranados, Carlos A.;Dunning, Andrew J.;Talbot, H. Keipp
背景：开发高剂量三价流感疫苗是为了改善老年人对流感疫苗的抗体反应，因此可能对这一人群中流感相关的发病率和死亡率产生有利影响。方法：采用IIIb期、多中心、随机、双盲、对照试验，比较高剂量（HD）三价流感灭活疫苗（每株血凝素60 μ g）与标准剂量（SD）疫苗（每株血凝素15 μ g）在65岁成人中的应用。在与H1N1大流行同时发生的2009-2010年流感季节，对安全性（严重不良事件[SAE]）、免疫原性（血凝抑制[HAI]滴度）和相对疗效进行了评估。结果：美国99个研究中心共纳入9172名参与者（分别为6117名和3055名随机分为HD组和SD组）。在疫苗接种后180天内，HD和SD疫苗组分别有6.7%和6.5%的参与者经历了至少一次SAE，其中0.4%和0.3%有致命的结果。两组中共有0.5%的受试者因SAE而终止研究。HD组接种后血凝素滴度及血凝素滴度>= 1:40率显著增高。没有观察到由与疫苗相似的病毒类型/亚型引起的流感病例。所有具有遗传或抗原性特征的病例均被归类为与大流行毒株甲型流感/加利福尼亚/7/2009 （H1N1）相似。在意向治疗分析中，HD疫苗相对于SD疫苗对任何流感病毒类型/亚型的疫苗效力为12.6% （95% CI -140.5; 65.8）。结论：与标准剂量流感灭活疫苗相比，高剂量三价流感灭活疫苗安全、耐受性好，具有较好的免疫应答。要证明疫苗的优越性，需要进行单独的大型随机对照试验。(c) 2012 Elsevier Ltd.版权所有。
Background: High-dose trivalent influenza vaccine was developed to improve antibody responses to influenza vaccine in the elderly and hence potentially impact favorably on influenza-associated morbidity and mortality in this population.Methods: A phase IIIb, multicenter, randomized, double-blind, controlled trial was conducted to compare High-Dose (HD) trivalent inactivated influenza vaccine (60 mu g of hemagglutinin [HA] per strain) to standard dose (SD) vaccine (15 mu g of HA per strain) in adults >= 65 years of age. Assessments of safety (serious adverse events [SAE]), immunogenicity (hemagglutination inhibition [HAI] titers) and relative efficacy were performed during the 2009-2010 influenza season, which coincided with the H1N1 pandemic.Results: A total of 9172 participants were enrolled in 99 research centers in the US (6117 and 3055 randomized to the HD and SD groups, respectively). Within 180 days after vaccination, 6.7% and 6.5% of participants in the HD and SD vaccine groups, respectively, experienced at least one SAE, of which 0.4% and 0.3% had a fatal outcome. A total of 0.5% of participants in both groups discontinued the study due to a SAE. Post-vaccination HAI titers and rate of post-vaccination HAI titer >= 1:40 were significantly higher in the HD group. No cases of influenza caused by viral types/subtypes similar to those in the vaccines were observed. All cases genetically or antigenically characterized were classified as similar to influenza A/California/7/2009 (H1N1), the pandemic strain. The vaccine efficacy of HD vaccine relative to SD vaccine against any influenza viral type/subtype was 12.6% (95% CI -140.5; 65.8) in the intent-to-treat analysis.Conclusion: High-dose trivalent inactivated influenza vaccine is safe and well tolerated and provides superior immune responses compared to standard dose vaccine. Demonstration of a superior vaccine efficacy requires a separate large randomized, controlled trial. (c) 2012 Elsevier Ltd. All rights reserved.