一项随机、双盲对照3期试验，比较高剂量和标准剂量流感疫苗在65岁及以上成年人中的免疫原性。

Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older.

作者信息

Falsey Ann R, Treanor John J, Tornieporth Nadia, Capellan Jose, Gorse Geoffrey J

机构信息

Department of Medicine, Rochester General Hospital, Rochester, NY, USA.

出版信息

J Infect Dis. 2009 Jul 15;200(2):172-80. doi: 10.1086/599790.

DOI:10.1086/599790

PMID:19508159

Abstract

BACKGROUND

Influenza-associated morbidity and mortality has not decreased in the last decade, despite increased receipt of vaccine. To improve the immunogenicity of influenza vaccine, a high-dose (HD) trivalent, inactivated influenza vaccine was developed.

METHODS

A multicenter, randomized, double-blind controlled study was conducted to compare HD vaccine (which contains 60 microg of hemagglutinin per strain) with the licensed standard-dose (SD) vaccine (which contains 15 microg of hemagglutinin per strain) in adults > or = 65 years of age.

RESULTS

HD vaccine was administered to 2575 subjects, and SD vaccine was administered to 1262 subjects. There was a statistically significant increase in the rates of seroconversion and mean hemagglutination inhibition titers at day 28 after vaccination among those who received HD vaccine, compared with those who received SD vaccine. Mean postvaccination titers for individuals who received HD vaccine were 116 for H1N1, 609 for H3N2, and 69 for B strain; for those who received SD vaccine, mean postvaccination titers were as 67 for H1N1, 333 for H3N2, and 52 for B strain. The HD vaccine met superiority criteria for both A strains, and the responses for B strain met non-inferiority criteria. Seroprotection rates were also higher for those who received HD vaccine than for those who received SD vaccine vaccine, for all strains. Local reactions were more frequent in individuals who received HD vaccine, but the reactions were mild to moderate.

CONCLUSIONS

There was a statistically significant increase in the level of antibody response induced by HD influenza vaccine, compared with that induced by SD vaccine, without an attendant increase in the rate or severity of clinically relevant adverse reactions. These results suggest that the high-dose vaccine may provide improved protective benefits for older adults.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT00391053 .

摘要

背景

尽管疫苗接种率有所提高，但过去十年中与流感相关的发病率和死亡率并未下降。为提高流感疫苗的免疫原性，研发了一种高剂量（HD）三价灭活流感疫苗。

方法

开展了一项多中心、随机、双盲对照研究，在65岁及以上成年人中比较HD疫苗（每株含60微克血凝素）与已获许可的标准剂量（SD）疫苗（每株含15微克血凝素）。

结果

2575名受试者接种了HD疫苗，1262名受试者接种了SD疫苗。与接种SD疫苗的受试者相比，接种HD疫苗的受试者在接种后第28天的血清转化率和平均血凝抑制滴度有统计学显著提高。接种HD疫苗个体的接种后平均滴度，H1N1为116、H3N2为609、B株为69；接种SD疫苗个体的接种后平均滴度，H1N1为67、H3N2为333、B株为52。HD疫苗对两种A型毒株均符合优效性标准，对B株的反应符合非劣效性标准。所有毒株中，接种HD疫苗者的血清保护率也高于接种SD疫苗者。接种HD疫苗个体的局部反应更频繁，但反应为轻至中度。