一种灭活的、含佐剂的大流行性流感（H5N1）原型疫苗的免疫原性、安全性及交叉反应性：一项II期双盲随机试验

Immunogenicity, safety, and cross-reactivity of an inactivated, adjuvanted, prototype pandemic influenza (H5N1) vaccine: a phase II, double-blind, randomized trial.

作者信息

Wu Jiang, Fang Han-Hua, Chen Jiang-Ting, Zhou Ji-Chen, Feng Zi-Jian, Li Chang-Gui, Qiu Yuan-Zheng, Liu Yan, Lu Min, Liu Li-Ying, Dong Shan-Shan, Gao Qiang, Zhang Xiao-Mei, Wang Nan, Yin Wei-Dong, Dong Xiao-Ping

机构信息

Beijing Centers for Diseases Control and Prevention, Beijing, China.

出版信息

Clin Infect Dis. 2009 Apr 15;48(8):1087-95. doi: 10.1086/597401.

DOI:10.1086/597401

PMID:19281330

Abstract

BACKGROUND

Avian influenza A virus H5N1 has the potential to cause a pandemic. Adjuvants and whole-virion vaccines are regarded as antigen sparing for pandemic vaccines.

METHODS

A double-blind, randomized trial was performed from 28 August to 22 December 2007 in 402 adults; 301 adults were randomly assigned to receive 2 doses of an inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine containing 5, 10, or 15 microg of hemagglutinin per dose 28 days apart, and 101 of them received 2 doses of 10 microg of vaccine 14 days apart. The vaccine was manufactured from the recombinant A/Vietman/1194/2004 (NIBRG14) strain. Blood samples were collected for hemagglutination inhibition and microneutralization assays.

RESULTS

All formulations were well tolerated, with no serious adverse events. Most local and systemic reactions were mild or moderate. Immune responses were induced after 1 dose in all vaccination groups. The highest immune response was seen after 2 doses of 15 microg of vaccine, with 90% and 100% seroconversion rates and 90% and 100% of participants having a titer of > or = 1:40 for hemagglutination inhibition and microneutralization assays, respectively. Both the 10- and 15-microg doses met or exceeded European Union licensure criteria. Generally, higher immune responses were elicited in participants vaccinated 28 days apart than those vaccinated 14 days apart. Cross-reaction assays showed that after 2 doses of 10 microg of vaccine, 98% and 87% of participants had a microneutralization titer of > or = 1:40 against heterologous Indonesia and Anhui strains, respectively.

CONCLUSIONS

The inactivated, aluminum-adjuvanted, whole-virion H5N1 vaccine not only showed good immunogenicity and safety but also elicited significant cross-reactivity against heterologous H5N1 strains in clade 2.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT00535665.

摘要

背景

甲型H5N1禽流感病毒有可能引发大流行。佐剂和全病毒疫苗被视为大流行疫苗的抗原节约型疫苗。

方法

2007年8月28日至12月22日对402名成年人进行了一项双盲随机试验；301名成年人被随机分配接受2剂灭活的、含铝佐剂的全病毒H5N1疫苗，每剂含5、10或15微克血凝素，间隔28天接种，其中101人接受2剂10微克疫苗，间隔14天接种。该疫苗由重组A/越南/1194/2004（NIBRG14）毒株制备。采集血样进行血凝抑制和微量中和试验。

结果

所有配方耐受性良好，无严重不良事件。大多数局部和全身反应为轻度或中度。所有疫苗接种组在接种1剂后均诱导出免疫反应。接种2剂15微克疫苗后免疫反应最高，血凝抑制试验和微量中和试验的血清转化率分别为90%和100%，90%和100%的参与者血凝抑制试验和微量中和试验的滴度≥1:40。10微克和15微克剂量均达到或超过欧盟许可标准。一般来说，间隔28天接种疫苗的参与者比间隔14天接种疫苗的参与者产生更高的免疫反应。交叉反应试验表明，接种2剂10微克疫苗后，分别有98%和87%的参与者对异源印度尼西亚株和安徽株的微量中和滴度≥1:40。