甲型H1N1流感病毒裂解疫苗的免疫原性和安全性

Immunogenicity and safety of pandemic influenza A H1N1 vaccine

目的：评价甲型H1N1流感病毒裂解疫苗（简称甲型H1N1流感疫苗）的免疫原性和安全性。方法按照随机、双盲、安慰剂对照的原则，采用0、21天免疫程序，选择3岁及3岁以上健康者1202人。分组为3～11岁、12～17岁、≥60岁组，按照人数基本为1∶1的比例随机分别接种7．5μg和15．0μg 甲型H1N1流感疫苗；18～59岁组按照人数基本为1∶1∶1的比例随机分别接种7．5μg、15．0μg甲型 H1 N1流感疫苗和安慰剂对照。观察各组接种后的不良反应率以及免疫前后血凝抑制（ HI）抗体阳转率、保护率、GMT水平和平均增长倍数。结果受试对象的安全性结果显示7．5μg和15．0μg组不良反应发生率分别为8．74％（48／549）和13．88％（74／533），其中Ⅱ级反应率分别为03．6％（2／549）和1．13％（6／533），未观察到Ⅲ级及以上不良反应和其他异常反应及严重不良事件。2剂接种未见不良反应叠加现象。7．5μg或15．0μg试验疫苗首剂免疫后，血清抗体阳性率分别为85．13％（395／464）和90．77％（413／455），保护率分别为85．56％（397／464）和91．43％（416／455），抗体GMT较免疫前分别增长36．1倍和526．倍。2剂免疫后，血清抗体阳性率分别是97．84％（454／464）和99．12％（451／455），保护率分别是98．06％（455／464）和99．56％（453／455），抗体GMT较免疫前分别增长63．3倍和96．0倍。4个年龄组（3～11岁、12～17岁、18～59岁及≥60岁年龄组）7．5μg和15．0μg组HI抗体阳性率和保护率均大于70％，GMT较免疫前均增长2．5倍以上，结果显示7．5μg和15．0μg甲型H1N1流感疫苗接种1剂后抗体水平已达到研究方案中设定的预期标准，免疫2剂后抗体阳性率和抗体水平明显提高。结论临床试验表明甲型H1 N1流感疫苗具有良好的安全性和免疫原性，且接种1剂15．0μg甲型H 1N1流感疫苗，即可在3岁和3岁以上人群中产生良好的免疫效果。

Objective To evaluate the safety and immunogenicity of pandemic influenza A （H1N1）vaccines.Methods Based on a random, double blind trial with a placebo as a cotrol, a total of 1 202 healthy individuals with an age ≥three years were divided into groups as 3 to 11 years of age ,12 to 17 years of age , and ≥60 years of age group, separately. 7.5 μg or 15.0 μg of influenza A （H1N1）vaccines were injected into subjects in above three groups separately and ran-domly, with a basic propotion （1 ∶1） for two parts of subjects.7.5μg or 15.0μg of influenza A （H1N1）vaccine or steri-lized water for injection as a placebo were injected into subjects in group for 18 to 59 years of age, separately and randomly, with a basic propotion （1 ∶1 ∶1） for three parts of subjects.The observation was carried out in total adverse reaction, and two doses, HI antibody positive conversion rate, protection rate（ HI antibody≧1 ∶40）, geometric mean titer （GMT） and its increased average times before and after immunization in each group.Results The safety result showed that adverse re-action rate was 8.74%（48/549）and 13.88%（74/533）in the group of 7.5μg and 15.0μg,respectively.Ⅱlevel adverse reaction rate was 0.36%（ 2/549 ） and 1.13% （ 6/533 ） respectively, in both parts, and ≥level Ⅲ adverse reaction, other abnormal reaction and serious adverse event did not occur in this trial.There was no overlaping of adverse reaction observed in immunization by the two doses.After immunization by the first dose of 7.5μg and 15μg, HI antibody positive rates were 85.13%（395/464）and 90.77%（413/455）, and pro-tection rates were 85.56%（397/464）and 91.43%（416/455）,HI antibody titer increased 36.1 times and 52.6 times,re-spectively.After immunization by the two doses, HI antibody positive rates were 97.84%（454/464）and 99.12%（451/455）, and protection rates were 98.06%（455/464）and 99.56%（453/455）, HI antibody titer increased 63.3 times and 96.0 times.respectively.Both HI antibody positive rate and protection rate were more than 70%, GMT increased by more 3.5 times than before immunization, in 7.5 μg and 15.0 μg parts in all four groups.The results showed that HI antibody reached to the expected level in the designed plan by a single immunization of one of both doses（ either 7.5 μg or 15.0μg）.Conclusion The clinical trail showed that a single 15.0μg dose of influenza A H1N1 vaccine was able to generate a good immuno response and had a good safety in subjects≥three years of age.