Huang L L, Xie Z Q, Zhang W, Zhang K, Wang Y X, Wang Z Q, Wu X J, Liu D M
Vaccine Clinical Research Center,Henan Provincial Center for Disease Control and Prevention, Zhengzhou 450016, China.
Hualan Biological Bacterin Inc., Xinxiang 453003, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2023 Feb 6;57(2):222-228. doi: 10.3760/cma.j.cn112150-20220314-00235.
To assess the safety and immunogenicity of freeze-dried rabies vaccine (Vero-cells) for human use on different immunization procedures in healthy people aged 9-65 years. A randomized, blind, positive-controlled clinical study was conducted in March 2015. The eligible residents aged 9-65 were recruited in Dengfeng city and Biyang County, Henan Province. A total of 1 956 subjects were enrolled. The subjects were randomly (1∶1∶1) assigned to 5-dose control group, 4-dose trial group and 5-dose trial group, with 652 subjects in each group. The subjects of 5-dose control group were immunized with control vaccine on days 0, 3, 7, 14 and 28. The subjects of 4-dose trial group were immunized with trial vaccine on days 0, 7 and 21 (2-1-1 phases) and the subjects of 5-dose trial group were immunized with trial vaccine on days 0, 3, 7, 14 and 28. A combination of regular follow-up and active reporting was used to observe local and systemic adverse reactions till 30 days after the first and full immunization, and the incidence rate of adverse reactions in three groups was analyzed and compared. The venous blood was collected before the first immunization, 7 days after the first immunization, 14 days after the first immunization and 14 days after the full immunization. The neutralizing antibody of rabies virus was detected by rapid fluorescent focus inhibition test (RFFIT), and the seropositive conversion rate and geometric mean concentration (GMC) of antibody were calculated. The adverse reaction rates in 5-dose control group, 4-dose trial group and 5-dose trial group were 41.87% (273/652), 35.43% (231/652) and 34.97% (228/652), respectively. The adverse reaction rates of 4-dose trial group and 5-dose trial group were lower than those of the 5-dose control group (<0.05). The local reactions were mainly pain, itching, swelling and redness in injection site, while the systemic reactions were mainly fever, fatigue, headache and muscle pain. The severity of adverse reactions was mainly mild (level 1), accounting for 85.33% (518/607), 89.02% (373/419) and 88.96% (427/480) of the total number of adverse reactions in each group. At 14 days after the first immunization and 14 days after the full immunization, the antibody positive conversion rates of three groups were all 100%. At 7 days, 14 days after the first immunization and 14 days after the full immunization, the GMCs of three groups were 0.60, 0.72, 0.59 IU/ml, 20.42, 23.99, 24.38 IU/ml and 22.95, 23.52, 24.72 IU/ml, respectively, with no significant difference (>0.05). The freeze-dried rabies vaccine (Vero-cells) for human use has good safety and immunogenicity when inoculated according to 5-dose and 4-dose immunization procedures.
评估人用冻干人用狂犬病疫苗（Vero细胞）在9至65岁健康人群中不同免疫程序的安全性和免疫原性。2015年3月开展了一项随机、盲法、阳性对照的临床研究。在河南省登封市和泌阳县招募符合条件的9至65岁居民。共纳入1956名受试者。受试者被随机（1∶1∶1）分配至5剂次对照组、4剂次试验组和5剂次试验组，每组652名受试者。5剂次对照组受试者于0、3、7、14和28天接种对照疫苗。4剂次试验组受试者于0、7和21天（2-1-1程序）接种试验疫苗，5剂次试验组受试者于0、3、7、14和28天接种试验疫苗。采用定期随访和主动报告相结合的方式，观察首次和全程免疫后30天内的局部和全身不良反应，并分析比较三组的不良反应发生率。在首次免疫前、首次免疫后7天、首次免疫后14天和全程免疫后14天采集静脉血。采用快速荧光灶抑制试验（RFFIT）检测狂犬病病毒中和抗体，并计算抗体阳转率和几何平均浓度（GMC）。5剂次对照组、4剂次试验组和5剂次试验组的不良反应发生率分别为41.87%（273/652）、35.43%（231/652）和34.97%（228/652）。4剂次试验组和5剂次试验组的不良反应发生率低于5剂次对照组（<0.05）。局部反应主要为注射部位疼痛、瘙痒、肿胀和发红，全身反应主要为发热、乏力、头痛和肌肉疼痛。不良反应严重程度主要为轻度（1级），分别占每组不良反应总数的85.33%（518/607）、89.02%（373/419）和88.96%（427/480）。在首次免疫后14天和全程免疫后14天，三组的抗体阳转率均为100%。在首次免疫后7天、14天和全程免疫后14天，三组的GMC分别为0.60、0.72、0.59 IU/ml，20.42、23.99、24.38 IU/ml和22.95、23.52、24.72 IU/ml，差异无统计学意义（>0.05）。人用冻干狂犬病疫苗（Vero细胞）按5剂次和4剂次免疫程序接种时具有良好的安全性和免疫原性。
