Ehrlich Hartmut J, Müller Markus, Oh Helen M L, Tambyah Paul A, Joukhadar Christian, Montomoli Emanuele, Fisher Dale, Berezuk Greg, Fritsch Sandor, Löw-Baselli Alexandra, Vartian Nina, Bobrovsky Roman, Pavlova Borislava G, Pöllabauer Eva Maria, Kistner Otfried, Barrett P Noel
Department of Global Research and Development, Baxter BioScience, Vienna, Austria.
N Engl J Med. 2008 Jun 12;358(24):2573-84. doi: 10.1056/NEJMoa073121.
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.
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 microg, 7.5 microg, 15 microg, or 30 microg of hemagglutinin antigen with alum adjuvant or 7.5 microg or 15 microg of hemagglutinin antigen without adjuvant. Serologic analysis was performed at baseline and on days 21 and 42.
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 microg and 15 microg 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.
A two-dose vaccine regimen of either 7.5 microg or 15 microg 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.)
禽流感H5N1病毒在禽类中广泛感染，且其向人类的传播有限，这表明该病毒有可能引发人类流感大流行。迫切需要一种对不同H5N1病毒株有效的H5N1疫苗。
在一项涉及六个亚组的随机、剂量递增的1期和2期研究中，我们调查了在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天的两次访视中，275名年龄在18至45岁之间的志愿者接受了两剂疫苗，每剂疫苗含有3.75微克、7.5微克、15微克或30微克血凝素抗原加明矾佐剂，或7.5微克或15微克无佐剂的血凝素抗原。在基线以及第21天和第42天进行血清学分析。
该疫苗不仅诱导了针对1类（A/越南/1203/2004）病毒株的中和免疫反应，还诱导了针对2类和3类毒株的中和免疫反应。使用佐剂并未改善抗体反应。不含佐剂、含有7.5微克和15微克血凝素抗原的制剂对疫苗株产生了最大反应。注射部位轻度疼痛（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。
不含佐剂、含有7.5微克或15微克血凝素抗原的两剂疫苗方案在高比例受试者中诱导了针对多种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。）
