期刊
VACCINE
卷 29, 期 31, 页码 4897-4902出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2011.05.001
关键词
Influenza; Vaccine; Recombinant; Toll-like receptor 5; Flagellin; Elderly
Background: Influenza vaccines perform poorly in the elderly with reduced serological response and vaccine efficacy. We evaluated a novel influenza vaccine consisting of the globular head of the HA1 domain of the A/Solomon Islands/3/2006 (H1N1) influenza virus (VAX125) genetically fused to the TLR5 ligand, flagellin, and produced in Escherichia coli. Methods: 120 subjects >= 65 years old were enrolled at three clinical centers. VAX125 vaccine was administered at doses of 0.5, 1, 2, 3, 5 or 8 mu g delivered i.m. as a single dose vaccination on Day 0 using a dose-escalation with 20 subjects in each dose level. Subjects were followed for adverse events and sera were tested by hemagglutination-inhibition (HAI) against egg-grown virus on days 0, 7, 14, and 28. Serum C-reactive protein (CRP) and anti-flagellin antibody were also assessed. Results: The mean age was 71 years. The vaccine was well tolerated at all dose levels, with no more than mild to moderate local or systemic symptoms. The geometric mean titers (GMT) increased in all dose groups. In the 5 mu g group the day 14 post-vaccination HAI titer was 1:226 showing a 12-fold increase over baseline. The 8 mu g group showed a similar post-vaccination GMT increase (similar to 8-fold). In the combined 5 and 8 mu g groups, the seroconversion rate was 75% and the seroprotection rate was 98%. Conclusions: A 5 mu g dose of VAX125 was safe and able to induce a greater than 10-fold increase HAI antibody levels and nearly complete seroprotection in subjects over 65 years old. The use of flagellin to adjuvant influenza vaccines via the TLR5 innate immune pathway appears to be a useful approach to overcome poor immune responses in the elderly. VAX125 is a promising new candidate for prevention of influenza A disease in both young adults and the elderly. (C) 2011 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据