上市后肠道病毒71型灭活疫苗的动物保护效果研究

Comparison of the protective efficacy of three different inactivated enterovirus 71 vaccines in mouse model

目的评价我国三家企业生产的肠道病毒71型(EV-A71)灭活疫苗的小鼠中和抗体应答水平和攻毒保护能力,为了解新上市EV-A71疫苗的免疫保护特性提供基础.方法应用小鼠模型,分别对上市的3家企业EV-A71灭活疫苗(编盲为A、B、C疫苗)进行中和抗体应答水平、被动免疫和主动免疫攻毒保护研究.结果一剂人用剂量A、B和C疫苗免疫后,EV-A71中和抗体几何均滴度(geometric mean titer,GMT)分别为331、132和69U/ml,A疫苗显著高于B疫苗和C疫苗(P<0.05).应用3家疫苗免疫血清被动保护,结果显示半数有效剂量(ED50)分别为1.9、50.4和8.2U/ml,提示3家疫苗免疫抗体均具有良好的保护能力,但随抗体稀释倍数的增加保护率下降趋势不同.EV-A71疫苗免疫主动保护结果显示,4倍稀释的3家EV-A71疫苗一针免疫即可获得100%的保护效果,但同样随剂量降低,保护率下降趋势不同,一针和二针免疫保护的ED50值分别为人用疫苗剂量的203.2、24.4和41.5倍,及396.4、121.4和127.5倍.结论我国不同厂家EV-A71灭活疫苗一针免疫即可获得良好的免疫应答和保护能力,抗体应答和保护水平与临床前研究一致,但三家疫苗特性存在一定差异,应进一步深入开展相关基础研究,充分保证上市后EV-A71疫苗的有效性.

Objective To evaluate the neutralizing antibody (NTAb) response levels and the ability of three en-terovirus 71(EV-A71) to protect mice from challenge with enterovirus 71in China.Methods The NTAb response levels and protective ability of three EV-A71inactivated vaccines (A,B and C vaccine) were studied in mouse model.Results After one human dosage injection of vaccine A,B,C,the GMTs of EV-A71 NTAb were 331,132and 69U/ml,respectively,and the difference between vaccine A and B,C was signifi-cant (P<0.05) .By using the immune serum from these three companies,the median effective doses (ED 50) of passive protection were 1.9,50.4and 8.2U/ml,respectively,and the declining trend of antibody positive rate was different with the increase of dilution rate.The protection of active immunization by EV-A71vaccine indicated that three types of four-fold diluted vaccine could achieve 100% protective efficacy by a single shot.However,with the declining of dosage,the declining trend of protection rate was different likewise.The ED 50 of a single shot were 203.2,24.4and 41.5times more than the vaccine dosage,respectively ; and the ED 50 of the two shots were 396.4,121.4and 127.5times,respectively.Conclusions The EV-A71inactivated vaccines from three different companies in China can result in favorable immune responses and achieve good protection efficacy by a single shot,and the levels of antibody responses and protection are consistent with the preclinical research.But differences in the characteristics of the three vaccines were found.Further basic researches should be carried out on immunological characteristics to ensure the effectiveness of vaccines after marketing.