A clinical trial of a whole-virus H5N1 vaccine derived from cell culture
A clinical trial of a whole-virus H5N1 vaccine derived from cell culture
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DOI：
10.1056/nejmoa073121
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发表时间：
2008-06-12
影响因子：
158.5
通讯作者：
Barrett, P. Noel
中科院分区：
文献类型：
--
作者：
Ehrlich, Hartmut J.;Mueller, Markus;Barrett, P. Noel
背景：禽流感 H5N1 病毒对禽类的广泛感染及其对人类的有限传播表明该病毒有可能引起人类流感大流行。迫切需要一种能有效对抗 H5N1 病毒不同毒株的 H5N1 疫苗。 方法：在一项涉及六个亚组的随机、剂量递增、1 期和 2 期研究中，我们研究了在 Vero 细胞培养物上生产的 H5N1 全病毒疫苗的安全性，并确定了其诱导能够中和各种 H5N1 毒株的抗体的能力。在相隔 21 天的两次访问中，275 名年龄在 18 至 45 岁之间的志愿者接受了两剂疫苗，每剂含有 3.75 μg、7.5 μg、15 μg 或 30 μg 血凝素抗原（含明矾佐剂）或 7.5 μg 或 15 μg 血凝素抗原（不含佐剂）。在基线以及第 21 天和 42 天进行血清学分析。结果：疫苗不仅诱导针对进化枝 1 (A/Vietnam/1203/2004) 病毒株的中和免疫反应，而且还针对进化枝 2 和 3 病毒株诱导中和免疫反应。佐剂的使用并没有改善抗体反应。使用含有7.5μg和15μg血凝素抗原而无佐剂的制剂获得了对疫苗株的最大反应。注射部位的轻度疼痛（9% 至 27% 的受试者）和头痛（6% 至 31% 的受试者）是所有疫苗制剂中最常见的不良事件。结论：7.5 μg 或 15 μg 血凝素抗原的两剂疫苗方案（不含佐剂）在高比例的受试者中诱导针对多种 H5N1 病毒株的中和抗体，表明这可能是一种有用的 H5N1 疫苗。 （ClinicalTrials.gov 编号，NCT00349141。）。
Background: Widespread infections of avian species with avian influenza H5N1 virus and its limited spread to humans suggest that the virus has the potential to cause a human influenza pandemic. An urgent need exists for an H5N1 vaccine that is effective against divergent strains of H5N1 virus.Methods: In a randomized, dose-escalation, phase 1 and 2 study involving six subgroups, we investigated the safety of an H5N1 whole-virus vaccine produced on Vero cell cultures and determined its ability to induce antibodies capable of neutralizing various H5N1 strains. In two visits 21 days apart, 275 volunteers between the ages of 18 and 45 years received two doses of vaccine that each contained 3.75 mu g, 7.5 mu g, 15 mu g, or 30 mu g of hemagglutinin antigen with alum adjuvant or 7.5 mu g or 15 mu g of hemagglutinin antigen without adjuvant. Serologic analysis was performed at baseline and on days 21 and 42.Results: The vaccine induced a neutralizing immune response not only against the clade 1 (A/Vietnam/1203/2004) virus strain but also against the clade 2 and 3 strains. The use of adjuvants did not improve the antibody response. Maximum responses to the vaccine strain were obtained with formulations containing 7.5 mu g and 15 mu g of hemagglutinin antigen without adjuvant. Mild pain at the injection site (in 9 to 27% of subjects) and headache (in 6 to 31% of subjects) were the most common adverse events identified for all vaccine formulations. Conclusions: A two-dose vaccine regimen of either 7.5 mu g or 15 mu g of hemagglutinin antigen without adjuvant induced neutralizing antibodies against diverse H5N1 virus strains in a high percentage of subjects, suggesting that this may be a useful H5N1 vaccine. (ClinicalTrials.gov number, NCT00349141.).