Objective: To compare the safety and immunogenicity of two different sequential schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV) followed by typeⅠ+Ⅲ bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC) form or liquid dosage form). Methods: This randomized, blinded, single center, parallel-group controlled trial was done from September 2015 to June 2016 in Liuzhou, Guangxi province. Healthy infants aged ≥2 months were eligible for enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules. According to the bOPV dosage form each sequential schedules, the subjects again were divided into drug candy(DC) form or liquid dosage form group, being 1sIPV+bOPV (DC)/1sIPV+2bOPV(liquid)/2sIPV+1bOPV(DC)/2sIPV+1bOPV(liquid). According to 0, 28, 56 d immunization schedule, Each group were given 3 doses. We recorded adverse events during the clinical trial (399 participants who receive at least one dose). 28 days post-Dose 3, we receive a total of 350 blood samples (excluding the quitters or subjects against trial plan), using cell culture trace against polio virus neutralization test Ⅰ, Ⅱ, Ⅲ neutralizing antibody (GMT), calculating the antibody positive rate.PolioⅠ,Ⅱand Ⅲ antibody titers were assessed by virus-neutralizing antibody assay and the seroconversion (4-fold increase in titer) from pre-Dose 1 to 28 days post-Dose 3 was calculated (total 350 samples) . Results: During the vaccination, the incidence of AEs in 1sIPV+2bOPV(DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV(DC), 2sIPV+1bOPV (liquid) group were 79%, 76%, 80% and 74% (χ(2)=1.23, P=0.747) , respectively. The severe AEs in groups were 6%, 5%, 6% and 4% (χ(2)=0.57, P=0.903) , respectively, and none was considered to be vaccination related. 28 days after 3(rd) vaccination, the seroconversion rates in 1sIPV+2bOPV (DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV (DC), 2sIPV+1bOPV (liquid) group, were 99%, 100%, 99% and 99% (χ(2)=0.94, P=0.815) , respectively, for type Ⅰ poliovirus; and 47%, 57%, 80%, 79% (χ(2)=31.56, P<0.001) , respectively, for type Ⅱ; and were 100%, 99%, 100%, 99% (χ(2)=2.02, P=0.568) , respectively, for type Ⅲ. In each group, the GMT of antibody against poliovirus typeⅠ were 4 539.68, 6 243.43, 6 819.53 and 7 916.29 (F=25.87, P<0.001) , respectively; Type Ⅱ were 12.98, 10.54, 63.75 and 84.21 (F=8.68, P=0.034) , respectively; Type Ⅲ were 1 172.55, 1 416.03, 2 648.89 and 3 250.75 (F=14.50, P=0.002) , respectively. Conclusion: On the same sequential schedules, there was no significant difference between the dosage forms, all of them showed good safety and immunogenicity. In the same dosage forms with different sequential schedules, the seroconversion rate was higher in 2 dose sIPV group than the 1 dose sIPV group, especially at the neutralizing antibody GMT level against polio type Ⅱ and Ⅲ after vaccination.
目的： 比较Ⅰ+Ⅲ型脊髓灰质炎减毒活疫苗（人二倍体细胞）（bOPV）糖丸和液体剂型与Sabin株脊髓灰质炎灭活疫苗（sIPV）联合序贯免疫接种在≥2月龄婴儿中的免疫原性和安全性。 方法： 于2015年9月至2016年6月，采用随机、盲法、单中心、平行对照设计，选择广西柳州市≥2月龄的婴儿为研究对象，将其分为1sIPV+2bOPV和2sIPV+1bOPV组，每种序贯免疫程序按bOPV剂型不同再分为糖丸剂型组与液体剂型组，即1sIPV+2bOPV糖丸组、1sIPV+2bOPV液体组、2sIPV+1bOPV糖丸组、2sIPV+1bOPV液体组，每组100名，按照0、28、56 d的免疫程序，共接种3剂。记录至少接种1剂次受试者（399名）不良反应事件；全程免疫后28 d，采集排除脱落者和违背试验方案者（共350名）血样，采用细胞培养微量中和试验测定抗脊灰病毒Ⅰ、Ⅱ、Ⅲ型中和抗体滴度（GMT），计算抗体阳转率，并对其进行统计学分析。 结果： 1sIPV+2bOPV糖丸组、1sIPV+2bOPV液体组、2sIPV+1bOPV糖丸组、2sIPV+1bOPV液体组全部不良反应发生率分别为79%（79/100）、76%（76/100）、80%（79/99）和74%（74/100）（χ(2)=1.23，P=0.747）；严重不良反应发生率分别为6%（6/100）、5%（5/100）、6%（6/99）和4%（4/100）（χ(2)=0.57，P=0.903）。全程免疫后，1sIPV+2bOPV糖丸组、1sIPV+2bOPV液体组、2sIPV+1bOPV糖丸组、2sIPV+1bOPV液体组Ⅰ型脊灰抗体阳转率分别为99%（86/87）、100%（83/83）、99%（87/88）、99%（91/92）（χ(2)=0.94，P=0.815），Ⅱ型分别为47%（41/87）、57%（47/83）、80%（70/88）、79%（73/92）（χ(2)=31.56，P<0.001），Ⅲ型分别为100%（87/87）、99%（82/83）、100%（88/88）、99%（91/92）（χ(2)=2.02，P=0.568）；Ⅰ型脊灰抗体GMT分别为4 539.68、6 243.43、6 819.53、7 916.29（F=25.87，P<0.001），Ⅱ型分别为12.98、10.54、63.75、84.21（F=8.68，P=0.034），Ⅲ型分别为1 172.55、1 416.03、2 648.89、3 250.75（F=14.50，P=0.002）。 结论： 相同序贯免疫程序中，bOPV糖丸剂型与液体剂型在≥2月龄的婴儿中均具有良好的安全性和免疫原性；相同剂型不同免疫程序中，2sIPV组较1sIPV组产生更高的血清中和抗体水平，尤其表现在Ⅱ型、Ⅲ型免疫后抗体GMT水平。.
Keywords: Dosage forms; Poliomyelitis; Poliovirus vaccine, inactivated.