人用狂犬病疫苗(地鼠肾细胞)的免疫原性评价

Study on immunogenicity of rabies vaccine(primary hamster Kidney cell)

目的研究狂犬病病毒aG株生产的人用狂犬病疫苗(地鼠肾细胞)免疫接种后抗体动态水平,评价疫苗的免疫原性,并对企业A和企业B生产的狂犬病疫苗进行效力评价。方法采用企业A和B生产的人用狂犬病疫苗(地鼠肾细胞)(简称狂苗)按暴露后免疫程序接种受试者,分别于免疫前、第1针免疫后3、7、14、42 d抽血并分离血清,用快速荧光灶抑制试验(rapid fluorescent focus inhibition test,RFFIT)检测中和抗体滴度,比较2组受试者血清样本的抗体阳转率和抗狂犬病中和抗体滴度;并对2015年1月至2023年3月企业A和企业B申报批签发的狂苗抽检效价结果进行回顾性分析,效力检测采用《中华人民共和国药典》(简称《中国药典》)2020版(三部)人用狂犬病疫苗效价测定法。结果企业A和企业B生产的狂苗第1针免疫后7 d抗体阳转率分别为50.6%、51.5%,14、42 d阳转率均为100%,抗体阳转率差异无统计学意义(χ^(2)=0.0161,P=0.899);第1针免后7 d中和抗体几何平均滴度(geometric mean titer,GMT)分别为1.5、2.2 IU/mL,差异无统计学意义(t=0.316,P=0.752);第1针免后14 d的GMT分别为5.7、8.7 IU/mL,差异无统计学意义(t=0.864,P=0.388);第1针免后42 d的GMT分别为9.7、9.8 IU/mL,差异无统计学意义(t=0.092,P=0.925)。参照《中国药典》2015版附录3503和《中国药典》2020版附录3503第一法(NIH法)检测的企业A和企业B的疫苗效价几何均值分别为6.8和6.0 IU/剂,差异无统计学意义(t=1.699,P=0.094)。参照《中国药典》2020版附录3503第二法(改良NIH法)检测的企业A和企业B生产的狂苗效价均≥4.0 IU/剂。结论2家企业利用狂犬病病毒aG株在原代地鼠肾细胞上生产的狂苗均可以及时地在人体内诱导产生保护性抗体,回顾分析表明效价检测结果全部符合规定,疫苗具有良好的免疫原性。

Objective To evaluate the immunogenicity of rabies vaccine for human use by studying the dynamic neutralizing antibody responses and vaccine potency of rabies vaccine produced by aG strain in Primary Hamster Kidney cell.Methods Rabies vaccines for human use(primary hamster kidney cell)(RV)from different manufactures A and B approved by NMPA were inoculated to subjects according to the post exposure vaccination procedure.Blood samples were collected at pre-immunization and day 3,7,14,42 after the first inoculation.Sera were isolated and tested with rapid fluorescent focus inhibition test(RFFIT)to calculate the neutralizing antibody titers.Positive seroconversion rates and neutralizing antibody GMT of subject sera vaccinated with two manufactures were compared;a retrospective analysis was also conducted to compare the vaccine potency of lot release of two manufactures from January 2015 to March 2023.Results The positive seroconversion rates of neutralizing antibody against rabies virus were 50.6%,51.5%at day 7 after the first inoculation separately,both were 100%at day 14 and day 42 after the first inoculation,with no significant difference in the positive seroconversion rates(χ^(2)=0.0161,P=0.899)between two manufactures;neutralizing antibody GMT were 1.5 IU/mL and 2.2 IU/mL at day 7 separately(t=0.316,P=0.752),5.7 IU/mL and 8.7 IU/mL at day 14 separately(t=0.864,P=0.388),9.7 IU/mL and 9.8 IU/mL at day 42 separately(t=0.092,P=0.925).According to NIH method of Appendix 3503 of 2015 edition and 2020 edition of Pharmacopoeia of the People's Republic of China,the geometric mean of vaccine potency of manufactures A and B were 6.8 IU/dose and 6.0 IU/dose respectively with no significant difference(t=1.699,P=0.094).According to the second method(Modified-NIH method)of Appendix 3503 of the 2020 edition of Pharmacopoeia of the People's Republic of China,the potency of the vaccines produced by manufactures A and B are all not less than 4.0 IU/dose.Conclusion The results indicated that rabies vaccine using aG strain produced in Primary hamster kidney cells could elicit protected antibodies rapidly.The retrospective analysis showed that the rabies vaccines all complied with the requirements and had good immunogenicity.